A Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus
Not Applicable
Recruiting
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Placebo
- Registration Number
- NCT07160257
- Lead Sponsor
- Amgen
- Brief Summary
The primary objective of this study is to determine the effect of maridebart cafraglutide relative to placebo on insulin sensitivity in participants with Type 2 Diabetes Mellitus (T2DM) treated with stable dose of metformin.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
Inclusion Criteria
- Informed consent before initiation of any study-specific activities/procedures.
- Male or female participants aged ≥ 18 and ≤ 70 years at the time of signing informed consent.
- Body mass index 27 ≥ and ≤ 45 kg/m^2 at screening.
- Diagnosis of T2DM at least 6 months before screening based on the WHO classification.
- Treatment of T2DM for at least 3 months prior to screening with diet and exercise and a stable dose of metformin (either immediate release or extended release), with or without a stable dose of 1 additional OAM other than metformin.
Exclusion Criteria
- Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other type of diabetes mellitus (except T2DM or history of gestational diabetes).
- History of proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment.
- One or more episodes of severe hypoglycemia (Level 3 hypoglycemia as defined by the American Diabetes Association classification criteria7 ) within 6 months before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery.
- Has modified diet or adopted any nutritional lifestyle modifications within 3 months prior to screening, as assessed by the investigator (or designee) based on participant self-report
- History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or breast ductal carcinoma in situ).
- Family (first-degree relative[s]) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).
- History or evidence of endocrine disorder (such as Cushing's syndrome) that can cause obesity.
- History or evidence of autoimmune disease that can directly or indirectly affect insulin production, insulin action, or glucose metabolism.
- History of any of the following within 90 days before screening: myocardial infarction, unstable angina, coronary artery bypass graft surgery or other major cardiovascular surgery, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure, or currently have New York Heart Association Class III or IV heart failure.
- History of chronic pancreatitis.
- History of acute pancreatitis within 6 months before screening.
- Positive human immunodeficiency virus test at screening.
- Evidence of hepatitis B or C infection based on 1 or more of the following results and/or criteria at screening
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation at screening or check-in (Day -4).
- Hemoglobin value < 12 g/dL (males) or < 11 g/dL (females) at screening or check-in (Day -4).
- Use within 90 days before randomization of medications, supplements, or alternative remedies for weight loss (eg, GLP-1RA, GIP agonists, phentermine/topiramate, naltrexone/bupropion, orlistat, and sympathomimetic drugs).
- Use within 90 days before randomization of chronic (> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations).
- Use within 90 days before randomization of medications that may cause significant weight gain including, but not limited to, tricyclic antidepressants, atypical antipsychotic, and mood stabilizers.
- Current or prior use of herbal supplements that affect insulin or glucose within 30 days before randomization.
- Currently receiving treatment in another investigational device or drug study, or less than 30 days (or 5 half-lives, whichever is longer) since ending treatment on another investigational device or drug study(ies).
- Participants of childbearing potential unwilling to adhere to contraception requirements during treatment and for an additional 16 weeks after the last dose of IMP.
- Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of IMP.
- Participants planning to become pregnant while on study through 16 weeks after the last dose of IMP.
- Major surgical procedure planned during the study.
- Participant has known sensitivity to any of the products or components to be administered during dosing.
- Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or medical monitor, if consulted as necessary, would pose a risk to participant's safety or interfere with the study evaluation, procedures, or completion.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Maridebart cafraglutide Maridebart cafraglutide Participants will receive maridebart cafraglutide subcutaneously (SC). Placebo Placebo Participants will receive placebo SC.
- Primary Outcome Measures
Name Time Method Change from Baseline in M-value from Hyperinsulinemic-euglycemic Clamp at Week 25 Baseline and Week 25
- Secondary Outcome Measures
Name Time Method Change from Baseline in Second Phase Insulin Secretion at Week 25 Baseline and Week 25 Measured as AUC of ISR from hyperglycemic clamp (ISR20-120min).
Change from Baseline in Body Weight at Week 25 Baseline and Week 25 Change from Baseline in Waist Circumference at Week 25 Baseline and Week 25 Change from Baseline in Hunger Fasting Appetite Visual Analog Scale (VAS) Score at Week 25 Baseline and Week 25 Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events Up to Week 41 Change from Baseline in First Phase Incremental ISR from Hyperglycemic Clamp (ISR0-8min) at Week 25 Baseline and Week 25 Change from Baseline in Maximum Insulin Secretion at 8 Minutes at Week 25 Baseline and Week 25 Measured as incremental ISR responses to arginine from hyperglycemic clamp at 8 minutes (ISRarg0-8min).
Change from Baseline in Maximum Insulin Secretion at 30 Minutes at Week 25 Baseline and Week 25 Measured as incremental ISR responses to arginine from hyperglycemic clamp at 30 minutes (ISRarg0-30min).
Change from Baseline in Hemoglobin A1c (HbA1c) at Week 25 Baseline and Week 25 Change from Baseline in Fasting Glucagon Concentration at Week 25 Baseline and Week 25 Change from Baseline in Glucagon Concentration During sMMTT (Total and Incremental AUC0-240min) at Week 25 Baseline and Week 25 Change from Baseline in Fasting Non-HDL-C at Week 25 Baseline and Week 25 Change from Baseline in Triglyceride Concentration During sMMTT (Total and Incremental AUC0-240min) at Week 25 Baseline and Week 25 Plasma Concentration of Maridebart Cafraglutide at Week 25 Week 25 Number of Participants with Anti-maridebart Cafraglutide Antibody Formation Up to Week 41 Change from Baseline in ISR at Week 25 Baseline and Week 25 Measured as total AUC (ISR0-240min) from standardized mixed meal tolerance test (sMMTT).
Change from Baseline in Clamp Disposition Index (cDI) at Week 25 Baseline and Week 25 Calculated as product of M-value and ISR0-120min from the hyperglycemic clamp.
Change from Baseline in Total Insulin Secretion at Week 25 Baseline and Week 25 Measured as area under the curve (AUC) of insulin secretion rate (ISR) from hyperglycemic clamp (ISR0-120min).
Change from Baseline in Post-meal Glucose Concentrations During sMMTT (Total and Incremental AUC0-240min) at Week 25 Baseline and Week 25 Change from Baseline in Fasting Free Fatty Acids (FFA) Concentration (During Hyperglycemic Clamp and sMMTT) at Week 25 Baseline and Week 25 Change from Baseline in FFA Concentrations During sMMTT (Total AUC0-240min) at Week 25 Baseline and Week 25 Change from Baseline in Percentage Body Fat at Week 25 Baseline and Week 25 Change from Baseline in Body Fat Mass at Week 25 Baseline and Week 25 Change from Baseline in Lean Body Mass at Week 25 Baseline and Week 25 Change from Baseline in Fasting Glucose Concentration at Week 25 Baseline and Week 25 Change from Baseline in Fasting Triglycerides at Week 25 Baseline and Week 25 Change from Baseline in Fasting High-density Lipoprotein-cholesterol (HDL-C) at Week 25 Baseline and Week 25 Change from Baseline in Satiety Fasting Appetite VAS Score at Week 25 Baseline and Week 25 Change from Baseline in Fullness Fasting Appetite VAS Score at Week 25 Baseline and Week 25 Change from Baseline in Prospective Food Consumption Fasting Appetite VAS Score at Week 25 Baseline and Week 25 Change from Baseline in Overall Fasting Appetite VAS Score at Week 25 Baseline and Week 25 Change from Baseline in Hunger Appetite VAS Score During sMMTT at Week 25 Baseline and Week 25 Change from Baseline in Satiety Appetite VAS Score During sMMTT at Week 25 Baseline and Week 25 Change from Baseline in Fullness Appetite VAS Score During sMMTT at Week 25 Baseline and Week 25 Change from Baseline in Prospective Food Consumption Appetite VAS Score During sMMTT at Week 25 Baseline and Week 25 Change from Baseline in Overall Appetite VAS Score During sMMTT at Week 25 Baseline and Week 25 Change from Baseline in Food Craving Inventory (FCI) Score at Week 25 Baseline and Week 25 Change from Baseline in Caloric Intake During Ad Libitum Meal at Week 25 Baseline and Week 25
Trial Locations
- Locations (1)
ProSciento
🇺🇸Chula Vista, California, United States
ProSciento🇺🇸Chula Vista, California, United States