Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus

Phase 2

Active, not recruiting

• Conditions: Type 2 Diabetes Mellitus; Overweight; Obesity
• Interventions: Biological: Maridebart Cafraglutide; Drug: Placebo

• Registration Number: NCT05669599
• Lead Sponsor: Amgen

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-20
• Study First Submitted QC: 2022-12-20
• Study First Posted: 2023-01-03
• Study Start: 2023-01-18
• Primary Completion: 2024-10-08
• Disposition First Posted: 2024-11-12
• Status Verified: 2025-02
• Disposition First Submitted: 2025-02-14
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-20
• Study Completion: 2026-01-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 592

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A: Maridebart Cafraglutide	Placebo	Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort A: Placebo	Placebo	Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts . Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort B: Maridebart Cafraglutide	Placebo	Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort B: Placebo	Placebo	Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort A: Maridebart Cafraglutide	Maridebart Cafraglutide	Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort B: Placebo	Maridebart Cafraglutide	Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort A: Placebo	Maridebart Cafraglutide	Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts . Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.
Cohort B: Maridebart Cafraglutide	Maridebart Cafraglutide	Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 52 in Body Weight	Baseline and Week 52

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 52 in Diastolic Blood Pressure (DBP)	Baseline and Week 52
Percent Change From Baseline to Week 52 in High-sensitivity C-reactive Protein (hs-CRP)	Baseline and Week 52
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	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
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
Percent Change From Baseline in Total Cholesterol	Baseline and Week 52
Percent Change From Baseline in non-HDL-C	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
Change from Baseline to Week 52 in Systolic Blood Pressure (SBP)	Baseline and Week 52
Change from Baseline to Week 52 in Body Mass Index (BMI)	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 Waist Circumference	Baseline and Week 52
Percent Change From Baseline in Very-low-density Lipoprotein Cholesterol (VLDL-C)	Baseline and Week 52
Percentage of Participants Achieving ≥ 5% Reduction in Body Weight From Baseline at Week 52	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 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
Change from Baseline to Week 52 in Body Weight	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 in High-density Lipoprotein Cholesterol (HDL-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

Trial Locations

Locations (78)

Alliance for Multispecialty Research Mobile; 🇺🇸 Mobile, Alabama, United States

Foothills Research Center; 🇺🇸 Phoenix, Arizona, United States

HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

Ark Clinical Research- Long Beach; 🇺🇸 Long Beach, California, United States

Ark Clinical Research- Tustin; 🇺🇸 Tustin, California, United States

Orange County Research Center; 🇺🇸 Tustin, California, United States

Diablo Clinical Research; 🇺🇸 Walnut Creek, California, United States

Alliance for Multispecialty Research Miami; 🇺🇸 Coral Gables, Florida, United States

Progressive Medical Research; 🇺🇸 Port Orange, Florida, United States

East-West Medical Research; 🇺🇸 Honolulu, Hawaii, United States

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