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

Study Overview
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Brief Summary
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The study aims to compare and assess the dose response of 3 selected doses of AMG 133 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).

Official Title
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A Phase 2 Randomized, Placebo-controlled, Double-blind, 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

Conditions
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Obesity, Overweight, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Biological: AMG 133
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: AMG 133<br>Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive AMG 133 or placebo in 1 of 7 dose cohorts. | Biological: AMG 133<br>* Participants will receive AMG 133 through 48 weeks.<br>|
| Placebo Comparator: Cohort A: Placebo<br>Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive AMG 133 or placebo in 1 of 7 dose cohorts. | Drug: Placebo<br>* Participants will receive placebo through 48 weeks.<br>|
| Experimental: Cohort B: AMG 133<br>Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive AMG 133 or placebo in 1 of 4 dose cohorts. | Biological: AMG 133<br>* Participants will receive AMG 133 through 48 weeks.<br>|
| Placebo Comparator: Cohort B: Placebo<br>Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive AMG 133 or placebo in 1 of 4 dose cohorts. | Drug: Placebo<br>* Participants will receive placebo through 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 52 in Body Weight |  | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 AMG 133 |  | Up to Week 64 | 
| Area Under the Concentration-time Curve (AUC) of AMG 133 |  | 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) | Analyzed in a subset of participants. | Baseline and Week 52 | 
| Change from Baseline to Week 52 in Lean Body Mass Using DEXA | Analyzed in a subset of participants. | Baseline and Week 52 | 
| 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 |