Obesity, Overweight, Type 2 Diabetes Mellitus
Conditions
Brief summary
The study aims to compare and assess the dose response of 3 selected doses of maridebart cafraglutide compared with placebo, on inducing and maintaining weight loss from baseline at Week 52 in participants with overweight or obesity without diabetes mellitus (Cohort A) and in participants with overweight or obesity with Type 2 diabetes mellitus (Cohort B).
Interventions
BIOLOGICALMaridebart Cafraglutide
Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.
DRUGPlacebo
Participants will receive placebo by SC injection.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at the time of signing informed consent. * BMI ≥30 kg/m\^2, or ≥27 kg/m\^2 and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease. * For participants in cohort B only, HbA1c ≥ 7% and ≤ 10% (53 to 86 mmol/mol) at screening with an established diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening and either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sulfonylurea, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor as monotherapy or combination therapy, per approved local label. * History of at least one unsuccessful dietary effort to lose body weight.
Exclusion criteria
* Change in body weight greater than 5 kg within 3 months prior to screening. * Obesity induced by other endocrinologic disorders. * History of pancreatitis. * Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2). * History of major depressive disorder within the last 2 years. * Any lifetime history of other major psychiatric disorder or suicide attempt.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline to Week 52 in Body Weight | Baseline and Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥ 5% Reduction in Body Weight From Baseline at Week 52 | Baseline and Week 52 | — |
| Percentage of Participants Achieving ≥ 10% Reduction in Body Weight From Baseline at Week 52 | Baseline and Week 52 | — |
| Achievement of ≥ 15% Reduction in Body Weight From Baseline at Week 52 | Baseline and Week 52 | — |
| Achievement of ≥ 20% Reduction in Body Weight From Baseline at Week 52 | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Hemoglobin A1c (HbA1c) | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Fasting Serum Insulin | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Fasting Plasma Glucose | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Homeostasis Model Assessment for Insulin Resistance (HOMA2-IR) | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Homeostasis Model Assessment for Steady State Beta Cell Function (HOMA2-%B) | Baseline and Week 52 | — |
| Maximum Observed Plasma Concentration (Cmax) of maridebart cafraglutide | Up to Week 64 | — |
| Area Under the Concentration-time Curve (AUC) of maridebart cafraglutide | Up to Week 64 | — |
| Change from Baseline to Week 52 in Waist Circumference | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Body Weight | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Systolic Blood Pressure (SBP) | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Diastolic Blood Pressure (DBP) | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Body Fat Mass Using Dual-energy X-ray Absorptiometry (DEXA) | Baseline and Week 52 | Analyzed in a subset of participants. |
| Change from Baseline to Week 52 in Lean Body Mass Using DEXA | Baseline and Week 52 | Analyzed in a subset of participants. |
| Percent Change From Baseline to Week 52 in High-sensitivity C-reactive Protein (hs-CRP) | Baseline and Week 52 | — |
| Change from Baseline to Week 52 in Body Mass Index (BMI) | Baseline and Week 52 | — |
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline and Week 52 | — |
| Percent Change From Baseline in Total Cholesterol | Baseline and Week 52 | — |
| Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | Baseline and Week 52 | — |
| Percent Change From Baseline in non-HDL-C | Baseline and Week 52 | — |
| Percent Change From Baseline in Very-low-density Lipoprotein Cholesterol (VLDL-C) | Baseline and Week 52 | — |
| Percent Change From Baseline in Triglycerides | Baseline and Week 52 | — |
| Percent Change From Baseline in Free Fatty Acids (FFA) | Baseline and Week 52 | — |
Countries
Australia, Canada, Czechia, Germany, Hong Kong, Hungary, Japan, Poland, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed