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within category "Diabetes & Hormones"
Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The
goal is to find the highest dose of MM-398 that can be given safely when it is used together
with the chemotherapy drug Cyclophosphamide.
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma,
neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid
Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of
a patient <18 years of age will provide informed consent and patients 11 to 18 years
of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for
pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability,
pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as
LOXO-292) administered orally to participants with advanced solid tumors, including
rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer
(MTC) and other tumors with RET activation.
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical benefit
from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years)
with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months
For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for
their tumor type and stage of disease, or in the opinion of the Investigator, would be
unlikely to tolerate or derive clinical benefit from appropriate standard of care
therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene
alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate
to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor
sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a thoracic
surgical oncologist, without prior systemic treatment for NSCLC
Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants
otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted Note: Potential exception for this exclusion criterion will require a valid
scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned
start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of participants receiving
radiation to more than 30% of the bone marrow or with a wide field of radiation, which
must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Participants are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds
(msec)
• Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.
• Participants with bundle branch block may be considered for study entry if QTc is
appropriate by a formula other than Fridericia's and if it is possible to monitor
for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
Testicular Tissue Cryopreservation for Fertility Preservation
Testicular tissue cryopreservation is an experimental procedure where a young boy's
testicular tissue is retrieved and frozen. This technique is reserved for young male patients
who are not yet producing mature sperm, with the ultimate goal that their tissue may be used
in the future to restore fertility when experimental techniques emerge from the research
pipeline.
• Be male at any age.
• Be scheduled to undergo surgery, chemotherapy, drug treatment and/or radiation for the
treatment or prevention of a medical condition or malignancy with risk of causing
permanent and complete loss of subsequent testicular function.
• Or, have a medical condition or malignancy that requires removal of all or part of one
or both testicles.
• Have newly diagnosed or recurrent disease. Those who were not enrolled at the time of
initial diagnosis (i.e., patients with recurrent disease) are eligible if they have
not previously received therapy that is viewed as likely to result in complete and
permanent loss of testicular function.
• Have two testicles if undergoing elective removal of all or part of a testicle for
fertility preservation only. Note: removal of both testicles will limit fertility
preservation options.
• Sign an approved informed consent and authorization permitting the release of personal
health information. The patient and/or the patient's legally authorized guardian must
acknowledge in writing that consent for specimen collection has been obtained, in
accordance with institutional policies approved by the U.S. Department of Health and
• Consent for serum screening tests for infectious diseases [HIV-1, HIV-2, Hepatitis B,
Hepatitis C], to be performed at the time of testicular tissue harvesting.
• Undergo a full history and physical examination and obtain standard pre-operative
clearance (based on the most recent ACC/AHA Guideline for Perioperative Cardiovascular
Evaluation for Noncardiac Surgery) as determined by their primary surgeon.
• Participating in long term follow-up is a requirement of the protocol.
Exclusion Criteria:
• Diagnosed with psychological, psychiatric, or other conditions which prevent giving
fully informed consent.
• Diagnosed with an underlying medical condition that significantly increases their risk
of complications from anesthesia and surgery.
Procedure: Testicular biopsy
Lymphoma, Sarcoma, Cancer, Mycosis Fungoides, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Male, Carcinoid Tumor, Cardiovascular, Colon, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Leukemia, Other, Hodgkins Lymphoma, Heart, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites, Autoimmune Disorders
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety
and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of
progression to overt heart failure.
• Type 2 Diabetes Mellitus
• Echocardiographic demonstration of diabetic cardiomyopathy
• Peak VO2 < 75% of predicted normal value based on age and gender
Exclusion Criteria:
• Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart
failure
• Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
• Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous
coronary intervention (PCI), coronary artery disease (CAD) or stroke
• Severe or moderate cardiac valve disease requiring intervention
• Clinically significant arrhythmia
• Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or
hypertrophic cardiomyopathy
• Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
• HbA1c >8.5% at screening
• Severe disease that would impact the performance of a cardio-pulmonary exercise test
Drug: AT-001, Drug: Placebo
Diabetic Cardiomyopathies
Type 2 Diabetes, Aldose Reductase Inhibitor, Stage B Heart Failure, Stage C Heart Failure, Cardiopulmonary Exercise Test
UT Southwestern; Parkland Health & Hospital System
Effect of SGLT2i on Cardiovascular Biomarkers in Patients With Type 2 Diabetes and CKD Stage 3b-4
This is a prospective, randomized double blind placebo controlled parallel group trial to
assess dapagliflozin on surrogate markers of kidney and cardiovascular health in patients
with stage 3b-4 Chronic Kidney Disease (CKD).
Randomization:
1) Dapagliflo3)zin 10mg (total dosage per day)
1) Placebo Dapagliflozin daily
This study includes three clinic in person visits and weekly telephone visits for 12 weeks.
1. Recruit 30 patients with CKD stages 3b-4 and randomize them in double-blind fashion to
either placebo or dapagliflozin 10mg daily for 12 weeks
2. Determine the effect of interventions on the primary outcome variable serum klotho
measured by immunoprecipitation-immunoblot
• 18-80 years of age
• All races and ethnicities
• All genders
• Type 2 diabetes mellitus
• History of hypertension defined as > 130 or > 80 mmHg or normotensive on pharmacologic
therapy
• Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2
(Stages 3b-4 CKD)
• Urinary albumin creatinine ratio of > 200 mg/g <5000mg/g
• Ability of study participant or legally authorized representative to provide informed
written consent
• Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days
post randomization.
Exclusion Criteria:
• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis
or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for
primary or secondary renal disease within 6 months prior to enrolment
• History of organ transplantation
• Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8
weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes (T1D)
• Active use of dapagliflozin
• History of persistent hypercalcemia (serum total Calcium > 10.5 mg/dl)
• Body mass index > 45 kg/m2
• Intolerance to magnesium supplementation
• Active on kidney transplant list
• Inability to provide informed consent
• Any condition outside the renal and cardiovascular disease area, such as but not
limited to malignancy, with a life expectancy of less than 2 years based on
investigator´s clinical judgement
• Active malignancy requiring treatment at the time of screening (with the exception of
successfully treated basal cell or treated squamous cell carcinoma).
• Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the
upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
• Women of child-bearing potential (ie, those who are not chemically or surgically
sterilized or who are not post-menopausal) who are not willing to use a medically
accepted method of contraception that is considered reliable in the judgment of the
investigator or women who have a positive pregnancy test at enrolment or randomization
or women who are breast-feeding
• Participation in another clinical study with an investigational product (IP) during
the last month prior to Enrolment
• Inability of the patient, in the opinion of the investigator, to understand and/or
comply with IP, procedures and/or follow-up OR any conditions that, in the opinion of
the investigator, may render the patient unable to complete the study. Patients who
cannot complete the patient reported outcome (PRO) assessments can still participate
in the study
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
Chlorthalidone (CTD) may produce various metabolic disturbances, including hypokalemia,
activation of Renin-Angiotensin- Aldosterone (RAA) system, oxidative stress, dyslipidemia,
Fibroblast growth factor 23 (FGF23) synthesis, and magnesium depletion. These factors may
interact with each other to contribute to the development of insulin resistances and
metabolic syndrome. Smaller studies have suggested that Potassium magnesium Citrate (KMgCit)
can ameliorate CTD- induced metabolic side effects independent of correction of hypokalemia.
This study will tests if KMgCit ameliorates CTD induced metabolic effects independent of
correction of hypokalemia.
Call 214-648-5940 danielle.pittman@utsouthwestern.edu or Call 214-648-5005 studyfinder@utsouthwestern.edu, Ashley.Murillo@UTSouthwestern.edu
Wanpen Vongpatanasin
17620
All
21 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02665117
STU 092015-058
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Treated or untreated stage I hypertension
Exclusion Criteria:
• Diabetes mellitus,
• Renal impairment (serum creatinine > 1.4 mg/dL),
• Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary
heart disease,
• Chronic regular NSAID use,
• Allergy to thiazide diuretics,
• Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents
or antacid more than once a week,
• Esophageal-gastric ulcer or history of gastrointestinal bleeding,
• Chronic diarrhea, vomiting,
• Excessive sweating,
• Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),
• Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase
(ALT) above upper limit of normal range),
• Subjects on any potassium supplement on a regular basis for any reason, such as
patients with primary aldosteronism,
• Pregnancy,
• History of major depression, bipolar disorder, or schizophrenia,
• History of substance abuse,
• Gout,
• Metabolic alkalosis, with serum bicarbonate > 32 meq/L,
• Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.
• Patient with Claustrophobia will not have MRI but can still participate in the study
without MRI
• Metal implants will not have MRI but can still participate in the study without MRI
A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW)
The researchers are doing this study to see if semaglutide can slow down the growth and
worsening of chronic kidney disease in people with type 2 diabetes. Participants will get
semaglutide (active medicine) or placebo ('dummy medicine'). This is known as participants'
study medicine - which treatment participants get is decided by chance. Semaglutide is a
medicine, doctors can prescribe in some countries for the treatment of type 2 diabetes.
Participants will get the study medicine in a pen. Participants will use the pen to inject
the medicine in a skin fold once a week. The study will close when there is enough
information collected to show clear result of the study. The total time participants will be
in this study is about 3 to 5 years, but it could be longer.
• Male or female, age above or equal to 18 years at the time of signing informed
consent. Japan: Male or female, age above or equal to 20 years at the time of signing
informed consent
• Diagnosed with type 2 diabetes mellitus
• HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol)
• Renal impairment defined either by:
1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to
75 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or
2. serum creatinine-based eGFR greater than or equal to 25 and less than 50
mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g
• Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone
system (RAAS) blocking agent including an angiotensin converting enzyme (ACE)
inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is
contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks
prior to the date of the laboratory assessments used for determination of the
inclusion criteria for renal impairment and kept stable until screening
Exclusion Criteria:
• Congenital or hereditary kidney diseases including polycystic kidney disease,
autoimmune kidney diseases including glomerulonephritis or congenital urinary tract
malformations
• Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to
screening
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or
transient ischaemic attack within 60 days prior to the day of screening
• Presently classified as being in New York Heart Association (NYHA) Class IV heart
failure
• Planned coronary, carotid or peripheral artery revascularisation
• Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal
dialysis
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within the past 90 days prior to screening or in the
period between screening and randomisation. Pharmacological pupil-dilation is a
requirement unless using a digital fundus photography camera specified for non-dilated
examination
Drug: Semaglutide, Drug: Placebo (semaglutide)
Diabetes Mellitus, Type 2, Kidney
UT Southwestern; Parkland Health & Hospital System
A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes (SOUL)
The researchers are doing this study to look whether the type 2 diabetes medicine,
semaglutide, has a positive effect on heart disease. Participants will either get semaglutide
tablets or placebo tablets ("dummy" medicine) - which treatment is decided by chance.
Participants must take one tablet with water every morning on an empty stomach and not eat or
drink anything for at least 30 minutes. The study will last for about 3.5-5 years.
Participants will have up to 25 clinic visits and 1 phone call with the study doctor. Women
cannot be in the study if pregnant, breast-feeding or if they plan to become pregnant during
the study period.
• Male or female, age equal to or above 50 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus
• HbA1c 6.5% •10.0% (47 •86 mmol/mol) (both inclusive) (latest available and no more
than 30 days old local laboratory assessment based on medical records or point of care
measurement)
• At least one of the below conditions (a-d):
a) Coronary heart disease defined as at least one of the following: i. Prior
myocardial infarction ii. Prior coronary revascularisation procedure iii. 50% or above
stenosis in coronary artery documented by cardiac catheterisation, computerized
tomography coronary angiography iv. Coronary heart disease with ischaemia documented
by stress test with any imaging modality b) Cerebrovascular disease defined as at
least one of the following: i. Prior stroke ii. Prior carotid artery revascularisation
procedure iii.50% or above stenosis in carotid artery documented by X-ray angiography,
magnetic resonance angiography, computerized tomography angiography or Doppler
ultrasound c) Symptomatic peripheral artery disease (PAD) defined as at least one of
the following: i. Intermittent claudication with an Ankle-brachial index (ABI) below
0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral
artery (excluding carotid) documented by X-ray angiography, magnetic resonance
angiography, computerized tomography angiography or Doppler ultrasound iii. Prior
peripheral artery (excluding carotid) revascularization procedure iv. Lower extremity
amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or
osteomyelitis) d) Chronic kidney disease defined as: i. eGFR below 60 mL/min/1.73 m^2
(based on medical records using latest available and no more than 6 months old
assessment)
Exclusion Criteria:
• Any of the following: myocardial infarction, stroke, hospitalisation for unstable
angina pectoris or transient ischaemic attack within the past 60 days prior to the day
of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of
screening
• Heart failure presently classified as being in New York Heart Association Class IV
• Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before
screening
Drug: Semaglutide, Drug: Placebo
Diabetes Mellitus, Type 2
UT Southwestern; Parkland Health & Hospital System
Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes (PIONEER PLUS)
This study compares three doses of once daily semaglutide tablets in people with type 2
diabetes who were previously treated with other oral anti-diabetic medicines. Participants
will be initiated on the lowest starting dose of 3 mg and gradually increased until they
reach the final trial dose of 14 mg, 25 mg or 50 mg once daily semaglutide tablets. The final
three doses will be randomized (i.e., decided by chance). Participants will be administered
one tablet per day for 68 weeks. Women cannot take part if they are pregnant, breast-feeding
or planning to become pregnant during the study period. Women who can get pregnant will be
checked for pregnancy via urine tests. Once daily semaglutide tablets (3 mg, 7 mg and 14 mg)
are approved for the treatment of type 2 diabetes in the US, in the EU and in some other
countries, under the brand name Rybelsus®.
• Male or female, age above or equal to 18 years at the time of signing informed
consent.
• Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of
screening.
• HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).
• BMI equal to or above 25 kg/m^2
• Stable daily dose(s) for 90 days prior to the day of screening of any of the following
treatment regimens:
• No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a
*:
• Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
• Sulfonylureas (SU) (equal to or above half of the maximum approved dose according
to local label or maximum tolerated or effective dose).
• Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).
• Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local
label).
• Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be
willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).
Exclusion Criteria:
• Treatment with any medication indicated for the treatment of diabetes or obesity other
than stated in the inclusion criteria within the past 90 days prior to the day of
screening. However, short term insulin treatment for a maximum of 14 days prior to the
day of screening is allowed.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of
below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving
global outcomes (KDIGO 2012) classification.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within the past 90 days prior to screening or in the
period between screening and randomisation. Pharmacological pupil-dilation is a
requirement unless using a digital fundus photography camera specified for non-dilated
examination.
A Trial to Investigate Long Term Efficacy and Safety of Lonapegsomatropin in Adults With Growth Hormone Deficiency
This is a phase 3 open-label multicenter extension study designed to evaluate the long-term
safety and efficacy of Lonapegsomatropin administered once-weekly. The study participants are
adults (males and females) with confirmed growth hormone deficiency (GHD) having completed
the treatment period in study TCH-306 (foresiGHt).
• Signing of the trial specific informed consent
• Completion of the treatment period and Visit 7 assessments of trial TCH-306, including
collection and upload of Visit 7 DXA scan
• Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial
hypertension or diabetic retinopathy stage 2 / moderate or above
Exclusion Criteria:
• Diabetes mellitus if any of the following are met:
1. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to
central laboratory at Visit 6 in trial TCH-306
2. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4
(DPP-4) inhibitors
• Active malignant disease or history of malignancy. Exceptions are:
1. Resection of in situ carcinoma of the cervix uteri
2. Complete eradication of squamous cell or basal cell carcinoma of the skin
• Known history of hypersensitivity and/or idiosyncrasy to the investigational product
(somatropin or excipients)
• Female who is pregnant, plans to become pregnant, or is breastfeeding
• Female participant of childbearing potential (i.e., fertile, following menarche and
until becoming post-menopausal unless permanently sterile) not willing throughout the
trial to use contraceptives as required by local law or practice. Details included in
Appendix 4/section 10.4 of the protocol
• Male participant not willing throughout the trial to use contraceptives as required by
local law or practice. Details included in Appendix 4/ section 10.4 of the protocol
• Any disease or condition that, in the judgement of the investigator, may make the
participant unlikely to comply with the requirements of the protocol or any condition
that presents undue risk from the investigational product or trial procedures
Drug: Lonapegsomatropin
Endocrine System Diseases, Adult Growth Hormone Deficiency, Hormone Deficiency, Other Endocrine System
• At least 18 years of age.
• Documented history of Type I or Type II Diabetes Mellitus requiring oral and/or
insulin replacement therapy.
• Presence of a DFU Wagner 2 grade wound on any aspect of the foot, provided it is at or
below the aspect of the medial malleolus. If two or more DFUs are present with the
same grade, the index ulcer is the largest ulcer and the only one evaluated in the
study.
• If other wounds are present on the same foot, they must be more than 2 cm distant from
the index ulcer.
• Index ulcer (i.e. current episode of ulceration) has been present for greater than
four weeks prior to the initial screening visit (SV1).
• Index ulcer (post-debridement) is a minimum of 1.0 cm2 and a maximum of 10 cm2 at the
first screening visit (SV1) and first treatment visit (RV1).
• Adequate circulation to the affected foot as documented by a dorsal transcutaneous
oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg,
or an Ankle Branchial Index (ABI) of ≥ 0.7 and ≤ 1.2 or Arterial Doppler with a
minimum of biphasic flow or Toe Brachial Index (TBI) ≥ 0.75 at SV1, using the affected
study extremity.
• Index ulcer and/or index ulcer limb may have had prior infection, but infection(s)
must be adequately treated and controlled as defined by IDSA Guidelines PEDIS Grade
level 1.
• The index ulcer has been offloaded with protocol defined offloading device throughout
the study screening period for at least 14 days prior to randomization (SV1 through
the first randomization visit (RV1)).
• Negative pregnancy test for females of childbearing potential (e.g., not post-
menopausal for at least one year or surgically sterile).
• Subject understands and is willing to participate in the clinical study and can comply
with weekly visits and the follow-up regimen.
• Females of childbearing potential must agree to use effective methods of contraception
(birth control pills, barriers, or abstinence) from screening through end of study
(EOS) and undergo pregnancy tests.
• Properly obtained written informed consent.
• Subject must have stable living environment in order to manage offloading and wound
care management.
• The index ulcer has a clean base and is free of necrotic debris at time of placement
of treatment product.
Exclusion Criteria:
• Index ulcer and/or index limb with presence of gangrene or unstable ischemia at
screening (SV1).
• Revascularization surgery on the lower extremity on which the index ulcer is located
within 30 days of screening (SV1).
• Index ulcer in the opinion of the investigator is suspicious for cancer and should
undergo an ulcer biopsy to rule out a neoplasm of the ulcer.
• Subjects with history of radiation on the same limb as the index ulcer (regardless of
time since last radiation treatment).
• Subjects with exposed internal fixation on the same limb as the index ulcer (note:
external fixation is allowed if deemed stable by the investigator).
• Subjects on any investigational drug(s) or therapeutic device(s) within 30 days
preceding the first screening visit (SV1).
• Index ulcer treated within the last 30 days prior to screening with a prohibited
treatment as defined in full protocol.
• Subjects with a history of more than two weeks treatment with immunosuppressants
(including systemic corticosteroids > 10mg prednisone (or equivalent) daily dose),
cytotoxic chemotherapy, or application of topical steroids to the index ulcer surface
within one month prior to first screening visit, or who receive such medications
during the screening period, or who are anticipated to require such medications during
the study.
• Presence of any condition(s) which seriously compromises the subject's ability to
complete this study or has a known history of poor adherence to medical treatment.
• In the opinion of the investigator, the subject is non-compliant with offloading or
index ulcer dressing prior to randomization.
• Active Charcot's arthropathy of the index ulcer limb as verified by clinical
evaluation, and/or imaging (x-ray or MRI) within 30 days prior to randomization.
• Subjects with chronic osteomyelitis and/or cellulitis on the same limb as the index
ulcer as verified by clinical evaluation, and/or imaging (x-ray or MRI) within 30 days
prior to randomization.
• Subject is pregnant or breast-feeding.
• Presence of diabetes with poor metabolic control as documented with an HbA1c ≥12.0
within 30 days of randomization (RV1).
• Subjects with end stage renal disease as evidenced by an eGFR <30 mL/min/1.73m2 within
120 days of randomization.
• Index ulcer has reduced or increased in area by 30% or more after 14 days of SOC from
SV1 to the RV1/randomization visit.
• Evidence of unstable human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis
C in the opinion of the investigator at first screening visit (SV1).
• Documented history of New York Heart Association Class III or IV congestive heart
failure or unstable cardiovascular disease requiring intervention within 60 days prior
to screening.
• Requiring surgical intervention (excluding debridement) at the time of consenting
and/or increased probability of requiring surgical intervention during study
participation (note: non-invasive surgical intervention is allowed if, per the
Principal Investigator, treatment will not affect subject's ability to participate in
clinical trial).
• Any clinically significant finding, in the judgment of the investigator, that would
place the subject at health risk, impact the study, or affect the completion of the
study.
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a
reduction in major adverse cardiac events (MACE) among participants hospitalized with
myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is
a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest,
cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or
incident heart failure.
1. Must have provided informed consent in a manner approved by the Investigator's
Institutional Review Board (IRB) prior to any study-related procedure being performed.
If a participant is unable to provide informed consent due to his/her medical
condition, the participant's legally authorized representative may consent on behalf
of the study participant, as permitted by local law and institutional Standard
Operating Procedures;
2. Aged greater than or equal to 18 years at the time of informed consent;
3. Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as
administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis),
alone or in combination with other cancer therapies (i.e. chemotherapy, radiation
therapy or targeted therapy). The FDA-approved ICI could be given as part of a
clinical trial but not in combination with a new investigational agent which may cause
myocarditis;
4. A diagnosis of myocarditis.
5. Hospitalized at the time of randomization;
6. On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg
of solumedrol per day for myocarditis within 24 hours of first administration of study
drug;
7. Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial
injury will be defined as an institutional troponin (either conventional or
high-sensitivity troponin I or T, using the standard institutional assay) with a value
that is ≥5 times the upper limit of the reference standard normal for that
institution. The troponin assay may be adjusted based on sex depending on
institutional standards. This value of troponin of ≥5 times above the institutional
upper limits of normal value must be noted within 10 days prior to potential
randomization. The 10-day period can be in the outpatient or inpatient setting. For
example, a participant with a troponin value that on one occasion was ≥5 times the
upper limits of institutional normal in the 10-day window prior to potential
randomization (whether in the inpatient or outpatient setting), but later decreases
below that threshold, typically due to starting corticosteroids, would still be
considered eligible;
8. The following laboratory parameters, not older than 48 hours at the time of
randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the
upper limit of the institutional normal ranges;
9. Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized)
must have a negative highly sensitive urine or serum pregnancy test prior to
randomization. Participating women of childbearing potential must be willing to
consistently use effective methods of contraception from screening until at least 90
days after administration of the last dose of study drug. Participating men must also
be willing to consistently use effective methods of contraception from screening until
at least 90 days after administration of the last dose of study drug; and
10. Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
1. Must not have experienced any of the following (as defined in the section on the
primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II
second degree atrioventricular block or third degree (complete) atrio-ventricular
(AV) block, for which an intervention with a temporary or permanent pacemaker is
completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or
sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a
ventricular tachyarrhythmia requiring intervention.
2. Recent (≤2 month) exposure to abatacept or belatacept.
3. Concurrent or recent (≤2 month) use of the following non-corticosteroid
immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors
(including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib),
tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The
use of intravenous immunoglobulin is permitted prior to randomization and during study
treatment.
4. Currently enrolled in another interventional study utilizing systemic agents for the
management of ICI-related toxicities.
5. Female who is pregnant, breastfeeding, or is considering becoming pregnant during the
study or for approximately 90 days after the last dose of study drug.
6. Male who is considering fathering a child or donating sperm during the study or for
approximately 30 days after the last dose of study drug.
7. Any active, chronic, or recurrent viral infection that, based on the investigator's
clinical assessment, makes the participant an unsuitable candidate for the study.
These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or
disseminated (even a single episode) herpes zoster, and disseminated (even a single
episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface
antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid
(DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody
(HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any
participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection
will be excluded. This is defined as the period of ongoing symptoms in the setting of
a positive Covid-19 test, or until 10 days after symptom onset and after resolution of
fever for at least 24 hours, without the use of fever-reducing medications.
8. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known
extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
9. Receipt of any live vaccine within four weeks prior to the first dose of study drug,
or expected need of live vaccination during study participation including at least 90
days after the last dose of IV study drug.
10. Any medical condition that could interfere with, or for which the treatment might
interfere with, the conduct of the study or interpretation of the study results, or
that would, in the opinion of the Investigator, increase the risk of the participant
by participating in the study.
11. Any factors that, in the Investigator's opinion, are likely to interfere with study
procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Small Intestine, Soft Tissue, Unknown Sites, Myocarditis Acute
A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes (FOCUS)
This study will look at the long-term effects of semaglutide (active medicine) on diabetic
eye disease when compared to placebo (dummy medicine). The study will be performed in people
with type 2 diabetes. Participants will either get semaglutide or placebo in addition to
their diabetes medicines - which treatment the participant gets is decided by chance.
Participants will inject the study medicine using a pen-injector. The medicine must be
injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last
for 5 years.
• Male or female, age greater than or equal to 18 years at the time of signing informed
consent
• Diagnosed with type 2 diabetes mellitus greater than or equal to 10 years prior to the
day of screening
• HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
• Eye inclusion criteria (both eyes must meet all criteria):
• Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive)
evaluated by fundus photography and confirmed by central reading centre
• No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema
twelve months prior to the day of screening
• No anticipated need for ocular or intraocular treatment for diabetic retinopathy or
diabetic macular oedema within six months after randomisation
• Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS
visual acuity protocol
• No previous treatment with pan-retinal laser photocoagulation
• No substantial non-diabetic ocular condition that, in the opinion of the
ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema
progression during the trial
• No substantial media opacities that would preclude successful imaging
Exclusion Criteria:
• Any of the following: myocardial infarction, stroke, hospitalization for unstable
angina pectoris or transient ischaemic attack within the past 60 days prior to the day
of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of
screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR
less than 30 ml/min/1.73 m^2
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or
medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of
screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Female who is pregnant, breast-feeding or intends to become pregnant or is of
child-bearing potential and not using highly effective contraceptive methods
• Current or previous (within 30 days before screening) treatment with any glucagon like
peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase-4 (DPP-4) inhibitor
• Receipt of any investigational medicinal product within 30 days before screening
• Previous participation in this trial. Participation is defined as randomisation
• Known or suspected hypersensitivity to trial products or related products
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or
compliance with the protocol
Drug: Semaglutide, Drug: Placebo (semaglutide)
Diabetes Mellitus, Type 2
UT Southwestern; Parkland Health & Hospital System
A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome (GRACE)
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess
the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous
Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance and/or
uncontrolled hypertension
• Has a confirmed diagnosis of endogenous Cushing syndrome
• Meets at least one of the following criteria:
• Has Type 2 diabetes mellitus
• Has impaired glucose tolerance
• Has hypertension
Exclusion Criteria:
• Has non-endogenous source of hypercortisolemia
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has poorly controlled diabetes mellitus
• Has severe renal insufficiency
Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (GRADIENT)
This is a Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy,
and safety of relacorilant to treat hypercortisolism in patients with cortisol-secreting
adrenal adenoma or hyperplasia associated with diabetes mellitus/ impaired glucose tolerance
and/or uncontrolled systolic hypertension.
• Shows lack of cortisol suppression
• Suppressed or low early-morning ACTH levels
• A radiologically confirmed adrenal lesion
• Has IGT or DM
• Has uncontrolled hypertension
Exclusion Criteria:
• Has severe, uncontrolled hypertension
• Has poorly controlled DM
• Has significantly abnormal liver test results or severe renal insufficiency
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 (TOPPLE T1D)
The trial is a placebo-controlled, double-blinded within cohorts, randomized, multiple
ascending dose trial with a sequential trial design. The primary outcome is to investigate
the safety and tolerability of ascending subcutaneous weekly doses of NNC0361-0041 plasmid in
patients with T1D.
1. Willing to provide Informed Consent
2. Participants must live in a location with rapid access to emergency medical services
3. Age 18-45 years (both inclusive) at the time of signing informed consent
4. Must have a diagnosis of T1D for less than 48 months at randomization
5. Must have at least one diabetes-related autoantibody present (GAD65A; mIAA, if
obtained within 10 days of the onset of insulin therapy; IA-2A; ICA; or ZnT8A)
6. Must have stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured
during an MMTT conducted at least 21 days from diagnosis of diabetes and within one
month (37 days) of randomization
7. Be willing to comply with intensive diabetes management
8. HbA1c ≤8.5% at screening
9. Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR
negative within 37 days of randomization and may not have had signs or symptoms of a
CMV and/or EBV compatible illness lasting longer than 7 days within 37 days of
randomization
10. Be up to date on recommended immunizations
11. Be at least 6 weeks from last live immunization
12. Be at least 4 weeks from killed vaccine other than flu vaccine
13. Participants are required to receive killed influenza vaccination at least 2 weeks
prior to randomization when vaccine for the current or upcoming flu season is
available
14. Be willing and medically acceptable to postpone live vaccines during the treatment
period and for 3 months following last dose of study drug
15. If participant is female with reproductive potential, she must have a negative
pregnancy test at screening and be willing to avoid pregnancy using a highly effective
contraceptive method for the 12 months of the study
16. Males of reproductive age must use adequate contraceptive method during the treatment
phase and for 3 months following last dose of study drug
17. Participants are required to receive an authorized non-live COVID-19 vaccination and
be fully vaccinated, including eligible boosters as indicated, at least two weeks
prior to randomization.
Exclusion Criteria:
Potential participants must not meet any of the following exclusion criteria:
1. One or more screening laboratory values as stated
1. Leukocytes < 3,000/μL
2. Neutrophils <1,500 /μL
3. Lymphocytes <800 /μL
4. Platelets <100,000 /μL
5. Haemoglobin <6.2 mmol/L (10.0 g/dL)
6. Potassium >5.5 mmol/L or <3.0 mmol/L
7. Sodium >150mmol/L or < 130mmol/L
8. AST or ALT ≥2.5 times the upper limits of normal
9. Bilirubin ≥ 1.5 times upper limit of normal
10. Glomerular Filtration Rate (eGFR) value of eGFR < 60 ml/min/1.73 m2 as defined by
KDIGO 2012 (43)
11. Any other laboratory abnormality that might, in the judgment of the investigator,
place the subject at unacceptable risk for participation in this trial
2. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control
within prior 7 days of screening
3. Use of other immunosuppressive agents including chronic use of systemic steroids.
Topical products are acceptable (nasal, conjunctival, skin)
4. Have active signs or symptoms of acute infection at the time of randomization
5. Have current, confirmed COVID-19 infection
6. Chronic active infection other than localized skin infections
7. Have evidence of prior or current tuberculosis infection as assessed by PPD,
interferon gamma release assay or by history
8. Have evidence of current or past HIV, Hepatitis B infection
9. Have evidence of active Hepatitis C infection
10. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4
weeks (except 2 weeks for flu vaccine)
11. Be currently pregnant or lactating, or anticipate getting pregnant within the one-year
study period.
12. Have severe obesity: adults BMI ≥ 40
13. Have a history of malignancies
14. Untreated hypothyroidism or active Graves' disease
15. History of severe reaction to prior vaccination
16. Participation in any clinical trial of an approved or non-approved investigational
medicinal product within 30 days after last blood draw (or 5 half-lives of
investigational drug, whichever is greater) before screening, or currently enrolled in
any other clinical trial
17. Subject is the investigator or any sub-investigator, research assistant, pharmacist,
study coordinator, other staff or relative thereof directly involved in the conduct of
the trial
18. Supine blood pressure at screening outside the range of 90-139 mmHg for systolic or
50-89 mmHg for diastolic. To exclude white-coat nervousness a single repeat
measurement is allowed
19. Have any complicating medical issues or abnormal clinical laboratory results that may
interfere with study conduct, or cause increased risk
20. Any condition that in the investigator's opinion may adversely affect study
participation or may compromise the study results
Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors
This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary
efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with
advanced solid tumors.
1. ≥ 18 years of age
2. Histopathological or cytologically documented locally advanced or metastatic solid
tumors who have no available standard therapeutic treatment options
3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Adequate organ function confirmed at screening and within 10 days of initiating
treatment, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelets (plt) ≥ 75 x 10^9/L
• AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver
metastases are present
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
6. Negative pregnancy test within 72 hours before starting study treatment in all
premenopausal women and women < 12 months after the onset of menopause
7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the
study and until at least 6 months after ceasing study treatment
8. Able to sign informed consent and comply with the protocol
Exclusion Criteria:
1. Women who are pregnant or lactating
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and
multiple myeloma
4. Patients with a history of primary central nervous system tumors or carcinomatous
meningitis.
5. Patients with the following mood disorders as judged by the Investigator or a
psychiatrist:
• Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm
to others)
• ≥ CTCAE grade 3 anxiety
6. Impaired cardiac function or significant diseases, including but not limited to any of
the following:
• left ventricular ejection fraction (LVEF) < 45% as determined by multigated
acquisition (MUGA) scan or echocardiogram (ECHO)
• Congenital long QT syndrome
• QTcF ≥ 480 msec on screening ECG
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute myocardial infarction ≤ 3 months prior to starting study drug
7. Patients with:
• unresolved diarrhea ≥ CTCAE grade 2, or
• impairment of gastrointestinal (GI) function, or
• GI disease that may significantly alter the absorption of TT-00420
8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or
uncontrolled infection) that could cause unacceptable safety risks or compromise
compliance with the protocol
9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks
(6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not
recovered from side effects of such therapy
10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
12. Patients who have been treated with any hematopoietic colony-stimulating growth
factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug.
13. Patients who are currently receiving treatment with therapeutic doses of warfarin
sodium or any other coumarin-derivative anticoagulants
14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study
drug or who have not recovered from the side effects of such treatment.
15. Patients who are currently receiving treatment with strong CYP3A inhibitors or
inducers ≤ 2 weeks prior to starting study drug.
16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
mandatory; patients with well controlled HIV might be enrolled)
17. Known history of active infection with Hepatitis B or Hepatitis C
18. Has received a live-virus vaccination within 30 days of planned first dose
19. Inability to swallow or tolerate oral medication
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that, in the opinion of the investigator, might confound the results of the trial,
interfere with the patient's safe participation and compliance in the trial.
Prostate Cancer, Sarcoma, Gastric Cancer, Bladder Cancer, Cholangiocarcinoma, Gallbladder Cancer, Thyroid Cancer, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Advanced Solid Tumor, Breast - Female, Breast - Male, Lung/Thoracic, Other Digestive Organ, Other Skin, Other Urinary, Prostate, Stomach, Thyroid, Small Intestine, Small-cell Lung Cancer
A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)
The main purpose of this study is to learn more about the safety, side effects, and
effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors
that have a change in a particular gene (known as the PIK3CA gene). Participation could last
up to 36 months (3 years) and possibly longer if the disease does not get worse.
• Have advanced breast cancer or another solid tumor with the presence of a PIK3CA
H1047R mutation (or other Sponsor and SRC-approved, activating PIK3CA mutations other
than H1047R mutation)
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for
enrollment if no tumor sample is available.
• Have stopped all cancer treatment and have recovered from the major side effects
• Have adequate organ function, as measured by blood tests
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
scale
• Patients must have
• Measurable disease
--- Patients with non-breast tumor types must have at least 1 measurable lesion
• Non-measurable bone disease (at least one bone lesion in breast cancer patients
only)
• For patients with an ER+ breast cancer diagnosis:
• If female, must be postmenopausal
• If male, must agree to use hormone suppression
• Phase 1a:
-- Dose escalation and backfill patients:
• Advanced solid tumor
• Patients may have had up to 5 prior regimens for advanced disease
• Phase 1b:
• Part A:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease
• Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
• Part B:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease.
• Part C:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
---- Prior CDK4/6 inhibitor therapy required.
• Have a diagnosis of diabetes mellitus Type 2
• Part D:
• Advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
• Part E:
• Advanced solid tumor
• Patients may have had up to 3 prior regimens for advanced disease
Exclusion Criteria:
• Medical Conditions
• Colorectal cancer
• Endometrial cancers with specific concurrent oncogenic alterations
• A history of known active or suspected
• Diabetes mellitus Type 1 or
• Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all
parts of Phase 1b except Part C).
• Serious concomitant systemic disorder
• Known or suspected history of untreated or uncontrolled central nervous system (CNS)
involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or
other clinically significant active disease process
• Prior exposure to PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
Breast Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Kaposis sarcoma, Small Intestine, Soft Tissue, Unknown Sites
Stereotactic Radiosurgery (SRS) for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true
tolerable doses, which may exceed the current standard doses. This may lead to an improvement
in local control, patient survival, and/or quality-of life.
Inclusion Criteria
1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ
cell cancer, or unknown primary tumor.
2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or
intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI
contrast, an MRI without contrast is acceptable if lesions are visible)
3. All brain metastases must be outside the brain stem (midbrain, pons and medulla).
4. Patient must have 10 or less brain metastases.
5. The maximum diameter of any lesion must be less than or equal to 3.0 cm.
6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any
targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one
additional brain metastasis that can be targeted with SRS
7. Age ≥ 18 years.
8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or
better.
9. All men, as well as women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring:
Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a
substance that kills sperm)
10. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria
1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
2. Patients with leptomeningeal metastasis.
NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive
CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal
involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal
enhancement by imaging (MRI) would be considered to have LMD even in the absence of
positive CSF cytology, unless a parenchymal lesion can adequately explain the
neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally
symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would
not be considered to have LMD. In that patient, CSF sampling is not required to
formally exclude LMD, but can be performed at the investigator's discretion based on
level of clinical suspicion.
3. Patients with a contraindication to both MRI (with or without contrast) and CT scan
(with contrast)
4. Patients with life expectancy < 3 months.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, would limit compliance with study requirements.
6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the
potential for congenital abnormalities and the potential of this regimen to harm
nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
A study to learn about safety and find out maximum tolerable dose of palbociclib given in
combination with chemotherapy (temozolomide with irinotecan or topotecan with
cyclophosphamide) in children, adolescents and young adults with recurrent or refractory
solid tumors (phase 1). Phase 2 to learn about the efficacy of palbociclib in combination
with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the
treatment of children, adolescents, and young adults with recurrent or refractory Ewing
sarcoma (EWS).
Inclusion:
1. Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed
relapsed or refractory solid tumor (including CNS tumors but not lymphomas).
Patients with Diffuse Intrinsic Pontine Glioma do not require histological only
radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed
or refractory solid tumor including but not limited to EWS, rhabdoid tumor,
rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse
Intrinsic Pontine Glioma do not require histological only radiographic confirmed
relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis
or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement.
Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners
is required OR availability of formalin fixed paraffin embedded (FFPE) tumor
tissue sample for central testing. Patient must have relapsed or have refractory
disease and at least evaluable disease in at least one site other than bone
marrow that can be followed by imaging.
2. Age ≥2 and <21 years at the time of study entry.
3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative
Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in
past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
5. Adequate renal function: Serum creatinine level based on age/gender must within
protocol specified limits.
6. Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to
disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's
syndrome.
7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have
measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS
disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of
the study are eligible with evaluable disease (eg, bone only disease with no soft
tissue component).
8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute
toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy,
differentiation therapy or biologic therapy, with the exception of alopecia.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and
at the baseline visit.
Exclusion:
1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination,
prior treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing regimen that includes TMZ. Patients who have received the combination
of IRN and TMZ and did not progress while on these medications are eligible. For
patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment
with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing
regimen that includes CTX. Patients who have received the combination of TOPO and CTX
and did not progress while on these medications are eligible. Phase 2 portion: prior
treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ
and did not progress while on these medications are eligible.
2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ
combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are
receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors
within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN
and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12
days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See
Section 5.7.1 for list of products.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for
nitrosoureas.
5. Prior irradiation to >50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5
half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line
placement are not considered major surgeries.
8. For IRN and TMZ with/without palbociclib combinations: known or suspected
hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with
TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
9. Patients with known symptomatic brain tumors or brain metastases and require steroids,
unless they have been on a stable or on a decreasing steroid dose for >14 days.
10. Patients with previously diagnosed brain metastases are eligible if they have
completed their prior treatment and have recovered from the acute effects of radiation
therapy or surgery prior to study entry for these metastases for at least 14 days post
radiation and 4 weeks post-surgery and are neurologically stable.
11. Hereditary bone marrow failure disorder.
12. QTc >470 msec.
13. History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart
failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia,
ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT
interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere
with absorption of orally administered drugs (eg, gastrectomy).
15. Severe acute or chronic medical or laboratory test abnormality that may increase the
risk associated with study participation or investigational product administration or
may interfere with the interpretation of study results, and in the judgment of the
Investigator, would make the patient inappropriate for entry into this study.
16. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
Neuroblastoma, Sarcoma, Solid Tumors, Ewing Sarcoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma, Rhabdomyosarcoma, Rhabdoid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Paricalcitol For Treatment of Secondary Hyperparathyroidism (SHPT) in Pediatric Participants With Stage 5 Chronic Kidney Disease (CKD)
The main objective of this study is to evaluate the safety, efficacy and pharmacokinetics of
paricalcitol oral solution in pediatric participants of ages 0 to 9 years with SHPT
associated with stage 5 CKD receiving Peritoneal Dialysis (PD) or Hemodialysis (HD). The
24-week study is divided into two 12-week dosing periods (Dosing Period 1 followed by Dosing
Period 2).
• Participant is currently diagnosed with and/or being treated for secondary
hyperparathyroidism (SHPT).
• Participant must be diagnosed with chronic kidney disease (CKD) stage 5 receiving
peritoneal dialysis (PD) or hemodialysis (HD) for at least 30 days prior to initial
Screening.
• For entry into the Washout Period (for vitamin D receptor activator [VDRA] non-naive
participants), the participant must meet the appropriate laboratory criteria based
upon the participant's age as described in the protocol.
• For entry into the Dosing Period (for VDRA-naive participants or VDRA non-naive
participants who have completed the Washout Period), the participant must meet the
appropriate laboratory criteria based upon the participant's age as described in the
protocol.
Exclusion Criteria:
• Participant is expected or scheduled to receive a kidney transplant within 6 months of
Screening or is a kidney transplant recipient.
• Participant is expected to discontinue peritoneal dialysis (PD) or hemodialysis (HD)
within 6 months of the initial Screening visit.
• Participant has had a parathyroidectomy within 12 weeks prior to Screening.
• Participant is taking maintenance calcitonin, bisphosphonates, glucocorticoids (in a
dose equivalent to more than > 0.16 mg/kg/day or 5 mg prednisone/day, whichever is
lower), 4 weeks prior to Dosing.
• Participant is receiving calcimimetics at the time of Screening or is expected to
initiate calcimimetics at any time throughout the study.
• Participant is unable to take oral medications.
Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-810 in
clinically stable patients (stable on standard of care treatment, e.g. diet ± ammonia
scavengers) with ornithine transcarbamylase deficiency (OTCD).
1. Adequate cognitive ability to consent and recall symptoms over a 1-week time period
2. Males and females ≥18 years of age with documented diagnosis of ornithine
transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to
consent to OTC gene sequencing and deletion/duplication testing
3. Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by
1. no clinical symptoms of hyperammonemia AND b,
2. an ammonia level <100 µmol/L (170 µg/dL) at the screening evaluation Subjects
must remain free from symptoms of hyperammonemia throughout the screening period.
4. If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in
dose or frequency) for ≥ 28 days prior to providing informed consent and throughout
the screening period
5. Must have maintained a stable protein-restricted diet (+/- amino acid supplementation)
for at least 28 days prior to providing informed consent and continue to maintain a
stable diet for the duration of the study
6. Good general health other than OTCD, in the opinion of the Investigator
7. Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before
study visits
8. Willingness to comply with procedures and visits
9. Willingness to follow contraception guidelines
Exclusion Criteria:
1. History of clinically significant disease(s), in the opinion of the Investigator
2. Clinically significant screening laboratory values
3. Uncontrolled diabetes
4. Clinically significant anemia
5. Subjects who develop infection during screening must be asymptomatic for at least 7
days prior to dosing
6. Unwillingness to comply with study requirements
7. History of positive HIV, hepatitis C, or chronic hepatitis B
8. Uncontrolled hypertension
9. Malignancy within 5 years prior to study
10. Treatment with another investigational drug, biological agent, or device within 30
days of screening, or 5 half-lives of investigational drug
11. Treatment with any oligonucleotide or mRNA within 6 months of screening, with
exceptions for some vaccinations and investigational treatments
12. History of gene therapy, hepatocyte or mesenchymal stem cell transplantation
13. Prior organ transplant
14. History of severe allergic reaction to a liposomal product
15. Recent history of, or current, drug or alcohol abuse
16. Dependence on inhaled (smoked or vaped) or oral cannabis products
17. Systemic corticosteroids within 6 weeks prior to screening
18. Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60
days of screening
19. Other conditions, in the opinion of the Investigator, that would make the subject
unsuitable for participation
A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 1)
This study compares insulin icodec (a new insulin taken once a week) to insulin glargine (an
insulin taken once daily which is already available on the market) in people with type 2
diabetes.
The study will look at how well insulin icodec taken weekly controls blood sugar compared to
insulin glargine taken daily. Participants will either get insulin icodec that participants
will have to inject once a week on the same day of the week or insulin glargine that
participants will have to inject once a day at the same time every day. Which treatment
participants get is decided by chance.
The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach. The
study will last for about 1 ½ years. Participants will have 37 clinic visits and 26 phone
calls with the study doctor. At 11 clinic visits participant will have blood samples taken.
At 8 clinic visits participants cannot eat or drink (except for water) for 8 hours before the
visit.
Participants will be asked to wear a sensor that measures the blood sugar all the time in 5
periods of about one month during the study (about 5 months in total). Women cannot take part
if pregnant, breast-feeding or plan to become pregnant during the study period.
• Male or female aged above or equal to 18 years at the time of signing informed
consent.
• Diagnosed with type 2 diabetes mellitus (T2D) 180 days or more prior to the day of
screening.
• HbA1c from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by
central laboratory analysis.
• Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to
the day of screening is allowed, as is prior insulin treatment for gestational
diabetes.
• Stable daily dose(s) 90 days or more prior to the day of screening of any of the
following anti-diabetic drug(s) or combination regimen(s): a. Any metformin
formulations at least or greater than 1500 mg or maximum tolerated or effective dose.
b. Any metformin combination formulations equal to or above 1500 mg or maximum
tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes
including combinations ((equal to or above half of the maximum approved dose according
to local label or maximum tolerated or effective dose): Sulfonylureas, Meglitinides
(glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2
(SGLT2) inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination
products (for the allowed individual oral anti-diabetic drugs), Oral or injectable
glucagon-like peptide 1 (GLP-1) receptor agonists
• Body mass index (BMI) equal to or below 40.0 kg/m^2.
Exclusion Criteria:
• Any episodes (as declared by the subject or in the medical records) of diabetic
ketoacidosis within 90 days prior to the day of screening.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or
transient ischaemic attack within 180 days prior to the day of screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at
screening.
• Anticipated initiation or change in concomitant medications (for more than 14
consecutive days) known to affect weight or glucose metabolism (e.g. treatment with
orlistat, thyroid hormones, or corticosteroids).
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within the past 90 days prior to screening or in the
period between screening and randomisation. Pharmacological pupil-dilation is a
requirement unless using a digital fundus photography camera specified for non-dilated
examination
Drug: Insulin icodec, Drug: Insulin glargine
Diabetes Mellitus, Type 2, Other Endocrine System, Pancreas
Celliant Socks to Increase Tissue Oxygenation and Complete Wound Closure in Diabetic Foot Wounds
This study is a prospective, multicenter, double-blind, 1:1 randomized clinical trial. The
purpose of this study is to demonstrate that the use of Celliant Socks increases tissue
oxygenation (via oxygen saturation, StO2) and incidence of wound closure in subjects with
diabetic foot ulcers. This study will use hyperspectral imaging and wound assessment to
measure these outcomes. The study will enroll 254 evaluable subjects total, 127 per arm to
meet the Primary Endpoint. Enrollment may continue up to twenty-five hundred (2500) evaluable
subjects total to meet the Key Secondary Endpoint of complete wound closure.
• Diagnosis of diabetes mellitus
• Subject is willing and able to wear a sports-style tube sock at least 22 hours a day.
• Ankle Brachial Index (ABI) ≥0.5 (bedside ABI is acceptable for screening purposes as
the formal imaging ABI may not be resulted prior to surgery) or toe pressure of
≥30mmHg
• One or more diabetic foot ulcers (only one will be treated) that are located in the
ankle area or below that has persisted a minimum of 30 days prior to the Screening
visit
• Diabetic Foot Ulcers ≥1cm2 and ≤16cm2
• Ulcer grade I or II, Stage A, I or II Stage B, according to University of Texas Wound
Classification System
• 22 years of age or older
Exclusion Criteria:
• Has clinically significant renal disease to require hemo or peritoneal dialysis
• Subject has untreated osteomyelitis
• Ulcers within 5cm of target ulcer or connected by fistulas
• Ulcer has decreased by 30% or more at the end of the run-in period
• Subject has untreated cellulitis
• Subject has untreated charcot
• Major immunodeficiency including HIV
• Is pregnant or plans to become pregnant
• Is nursing or actively lactating
• Developmental disability/significant psychological disorder that in the opinion of the
investigator could impair the subject's ability to provide informed consent,
participate in the study protocol or record study measures, including untreated
schizophrenia, bipolar disorder and psychiatric hospitalization within the last 2
years.
• Active alcohol or substance abuse in the opinion of the investigator that could impair
the subject's ability to provide informed consent, participate in the study protocol
or record study materials
Device: Celliant Diabetic Medical Socks, Device: Control (placebo) Medical Socks
Diabetic Foot Ulcer
UT Southwestern; Parkland Health & Hospital System
Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia (CAHtalyst)
This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont
versus placebo administered for 24 weeks in approximately 165 adult subjects with classic CAH
due to 21-hydroxylase deficiency. The study consists of a 6 month randomized, double blind,
placebo-controlled period, followed by 1 year of treatment with crinecerfont. Duration of
participation is approximately 20 months.
1. Be willing and able to adhere to the study procedures, including all requirements at
the study center and return for the follow-up visit.
2. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH.
3. Be on a stable regimen of steroidal treatment for CAH.
4. Patients of childbearing potential must agree to use hormonal or two forms of
nonhormonal contraception (dual contraception) or other highly effective contraception
during the study.
Exclusion Criteria:
1. Have a diagnosis of any of the other known forms of classic CAH.
2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition
requiring chronic glucocorticoid therapy.
3. Have a clinically significant unstable medical condition or chronic disease other than
CAH.
4. Have a history of cancer unless considered cured.
5. Are pregnant.
6. Have a known history of clinically significant arrhythmia or abnormalities on ECG.
7. Have a known hypersensitivity to any corticotropin releasing hormone antagonists.
8. Have received any other investigational drug within 30 days before initial screening
or plan to use an investigational drug (other than the study drug) during the study.
9. Have current substance dependence, or current substance (drug) or alcohol abuse.
10. Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior
to the study.
A Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency (foresiGHt)
A 38 week dosing trial of lonapegsomatropin, a long-acting growth hormone product,
administered once-a-week versus placebo-control. A daily somatropin product arm is also
included to assist clinical judgement on the trial results. Approximately 240 adults (males
and females) with growth hormone deficiency will be included. Randomization will occur in a
1:1:1 ratio (lonapegsomatropin : placebo : daily somatropin product). This is a global trial
that will be conducted in, but not limited to, the United States, Europe, and Asia.
Inclusion Criteria
1. Age between 23 and 75 years, inclusive, at screening.
2. AGHD Diagnosis Criteria
For adult-onset AGHD: documented history of structural hypothalamic-pituitary disease,
hypothalamic-pituitary surgery, cranial irradiation, 1-4 non-GH pituitary hormone
deficiencies, a proven genetic cause of GHD, or traumatic brain injury (TBI).
A. For all countries except Japan: Subjects must satisfy at least one of the following
criteria:
1. Insulin tolerance test: peak GH ≤5 ng/mL
2. Glucagon stimulation test according to body mass index (BMI)
• i. BMI ≤30 kg/m2: peak GH ≤3 ng/mL
• ii. BMI >30 kg/m2: peak GH ≤1 ng/mL
3. Three or four pituitary axis deficiencies (i.e., adrenal, thyroid, gonadal,
and/or vasopressin; not including GH) with IGF-1 SDS ≤ -2.0 at screening
4. Macimorelin test: peak GH ≤2.8 ng/mL
5. Growth hormone releasing hormone (GHRH) + arginine test according to BMI:
• i. BMI <25 kg/m2, peak GH <11 ng/mL
• ii. BMI ≥25-≤30 kg/m2, peak GH <8 ng/mL
• iii. BMI >30 kg/m2, peak GH <4 ng/mL
B. For Japan only: Subjects with adult onset AGHD and deficiency of one or more other
pituitary hormones need to satisfy at least one of the following criteria, while
subjects with isolated GHD and no evidence of intracranial structure disorder
(structural hypothalamic-pituitary disease) or with adult onset AGHD without
deficiency of other pituitary hormones need to satisfy at least 2 of the following
criteria:
1. Insulin tolerance test: peak GH ≤1.8 ng/mL
2. Glucagon test: peak GH ≤1.8 ng/mL
3. Growth Hormone Releasing Peptide-2 (GHRP-2) tolerance test: peak GH ≤9 ng/mL
3. IGF-1 SDS ≤ -1.0 at screening as measured by central laboratory.
4. hGH treatment naïve or no exposure to hGH therapy or GH secretagogue for at least 12
months prior to screening.
5. For subjects on hormone replacement therapies for any hormone deficiencies other than
GH (e.g., adrenal, thyroid, estrogen, testosterone) must be on adequate and stable
doses for ≥6 weeks prior to and throughout screening.
6. For subjects not on glucocorticoid replacement therapy, documentation of adequate
adrenal function at screening defined.
7. For males not on testosterone replacement therapy: morning (6:00 •10:00AM) total
testosterone within normal limits for age.
8. On a stable diet and exercise regime at screening with no intention to modify diet or
exercise pattern during the trial, i.e., no weight reduction program intended during
the trial or within the last 90 days prior to or through screening.
9. No plans to undergo bariatric surgery during the trial.
10. Normal fundoscopy at screening (without signs/symptoms of intracranial hypertension or
diabetic retinopathy above stage 2 / moderate). For subjects with a diagnosis of
diabetes mellitus at screening, this must be documented with a fundus photograph.
11. Able and willing to provide a written informed consent and authorization for protected
health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).
Exclusion Criteria
1. Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on
an endpoint.
2. Diabetes mellitus at screening if any of the following criteria are met:
1. Poorly controlled diabetes, defined as HbA1c >7.5% at screening.
2. Diabetes mellitus (defined as HbA1c ≥6.5% and/or fasting plasma glucose ≥126
mg/dL and/or plasma glucose ≥200 mg/dL two hours after oral glucose tolerance
test) diagnosed <26 weeks prior to screening
3. Change in diabetes regimen (includes dose adjustment) within <90 days prior and
throughout screening
4. Use of any diabetes drugs other than metformin and/or DPP-4 inhibitors for a
cumulative duration of greater than 4 weeks within 12 months prior to screening
5. Diabetes-related complications at screening (i.e., nephropathy as judged by the
investigator, neuropathy requiring pharmacological treatment, retinopathy stage 2
/ moderate and above within 90 days prior to screening or during screening)
3. Active malignant disease or history of malignancy. Exceptions to this exclusion
criterion:
1. Resection of in situ carcinoma of the cervix uteri
2. Complete eradication of squamous cell or basal cell carcinoma of the skin
3. Subjects with GHD attributed to treatment of intracranial malignant tumors or
leukemia, provided that a recurrence-free survival period of at least 5 years
prior to screening is documented in the subject's file based on a Magnetic
Resonance Imaging (MRI) result
4. Evidence of growth of pituitary adenoma or other benign intracranial tumor within the
last 12 months before screening.
5. Subjects with acromegaly without remission / with documented remission less than 24
months prior to screening.
6. Subjects with Cushing's disease without remission / with documented remission less
than 24 months prior to screening.
7. Subjects with prior cranial irradiation or hypothalamic-pituitary surgery: the
procedure took place less than 12 months prior to screening.
8. eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease
(MDRD) equation.
9. Hepatic transaminases (i.e., AST or ALT) >3 times the upper limit of normal.
10. Heart failure NYHA class 3 or greater (NYHA 1994).
11. QTcF ≥ 451 milliseconds on 12-lead ECG at screening.
12. Poorly controlled hypertension.
13. Cerebrovascular accident within 5 years prior to screening.
14. Anabolic steroids (other than gonadal steroid replacement therapy) or
oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout
screening.
15. Currently using or have used within 26 weeks prior to screening any weight-loss or
appetite-suppressive medications.
16. Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds
(somatropin) or excipients employed in this trial.
17. Known history of neutralizing anti-hGH antibodies.
18. Inability to undergo scanning by DXA or a non-interpretable DXA scan at screening.
19. Female who is pregnant, breast-feeding or intends to become pregnant or is of
childbearing potential and not using adequate contraceptive methods
20. Male subjects must use a condom, or his female partner of childbearing potential must
use an effective form of contraception as described above, from the beginning of
screening to the last trial visit.
21. Known substance abuse or known (or previous) eating disorders, including anorexia
nervosa, bulimia and severe gastrointestinal disease affecting normal eating (as
judged by the investigator).
22. Any disease or condition that, in the judgement of the investigator, may make the
subject unlikely to comply with the requirements of the trial or any condition that
presents undue risk from the investigational product or procedures.
23. Participation in another interventional clinical trial involving an investigational
compound within 26 weeks prior to screening or in parallel to this trial.
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating
loss of appetite in patients with cancer that has spread to other places in the body
(advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if
olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and
preventing weight loss.
• Women and men of reproductive potential should agree to use an appropriate method of
birth control throughout their participation in this study due to the teratogenic
potential of the therapy utilized in this trial. Appropriate methods of birth control
include abstinence, oral contraceptives, implantable hormonal contraceptives or double
barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or
physician-estimated caloric intake of less than 20 calories/kilogram of body weight
per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an
appetite score of 4 or worse on the "Please rate your appetite…." question that
requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of
registration
• Not currently using systemic adrenal steroids (with the exception of short-term
dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the
past month
• Patient should not have poorly controlled hypertension or congestive heart failure at
registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or
intractable vomiting (defined as vomiting more than 3 times per day over the preceding
week)
• Not currently using olanzapine for another medical condition or had previously used
olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may
have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had
left patients with compromised taste, which has not resolved at the time of
registration
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN)
• Fasting glucose > 1410 mg/dl
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine,
clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking
patients should have access to Spanish speaking staff on site or through the use of a
translation service to be able to conduct the informed consent discussion in Spanish,
and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency
virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the
patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia
or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate
cancer (this exclusion criterion is intended to circumvent any confounding
antineoplastic effects of megestrol acetate)
Safety and Efficacy of HMI-103, a Gene Editing Development Candidate in Adults With Classical PKU Due to PAH Deficiency
This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the
safety and efficacy of a single intravenous (I.V.) administration of HMI-103, a gene editing
development candidate, in adult participants aged 18 to 55 years, inclusive, with classical
PKU due to PAH deficiency who have uncontrolled disease despite Phe restricted dietary
management.
• Adults 18-55 years of age at the time of informed consent
• Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
• Four baseline plasma Phe values with a concentration of ≥ 600 μmol/L and at least one
historical value ≥ 600 μmol/L in the preceding 24 months.
• Participants must have uncontrolled classical PKU disease (despite Phe-restricted
dietary management) in the judgment of the investigator and confirmed by the
independent DMC at the end of the Screening period.
• Participant has the ability and willingness to maintain their baseline diet, for the
duration of the trial, unless otherwise directed
Exclusion Criteria:
• Subjects with PKU that is not due to PAH deficiency
• Presence of anti-AAVHSC15 neutralizing antibodies
• Participants who are well controlled on a Phe-restricted diet.
• Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
• Liver function tests > ULN
• International normalized ratio (INR) > 1.2
• Hematology values outside of the normal range
• Previously received gene therapy for the treatment of any condition.
Drug: HMI-103
Other Endocrine System, Phenylketonurias, PAH Deficiency, Phenylketonuria
A Research Study to Look Into How Well Semaglutide Medicine Works at Different Doses in People With Type 2 Diabetes and Overweight
This study compares how three doses of semaglutide work in participants with type 2 diabetes
(T2D) and overweight who are taking metformin. The study will look mainly at how well
participant's blood sugar and participant's body weight are controlled when they are taking
the study medicine at different doses. Participants will either get semaglutide [2 milligrams
(mg), 8 mg, or 16 mg] or semaglutide placebo (a dummy medicine). Participants will take the
study medicine with an injection pen called NovoPen®4. The injection pen is a medical tool
with a needle used to inject the study medicine under the skin. The study will last for about
52 weeks. Participants will have 13 clinic visits and 4 phone calls.
• Male or female.
• Aged 18-64 years (both inclusive) at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus greater than equal to (≥) 180 days prior to
the day of screening.
• Glycosylated haemoglobin (HbA1c) of 7.0 •10.5 percentage (%) [53 •91 millimoles per
mole (mmol/mol)] (both inclusive).
• Body Mass Index (BMI) ≥ 27.0 kilograms per meter square (kg/m^2).
• Stable daily dose(s) ≥ 90 days prior to the day of screening of any metformin
formulations.
Exclusion Criteria:
• Treatment with any medication for the indication of diabetes or obesity other than
stated in the inclusion criteria within 90 days before screening. However, short term
insulin treatment for a maximum of 14 days prior to the day of screening is allowed,
as is prior insulin treatment for gestational diabetes.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within the past 90 days prior to day of screening or in
the period between screening and randomisation. Pharmacological pupil-dilation is a
requirement unless using a digital fundus photography camera specified for non-dilated
examination.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less
than (<) 30 milliliters per minute (mL/min)/1.73 meter square (m^2) at screening.