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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 592
- 试验地点
- 78
- 主要终点
- Percent Change From Baseline to Week 52 in Body Weight
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort A: 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.
干预措施: Placebo (Drug)
Cohort A: 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.
干预措施: Placebo (Drug)
Cohort B: 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.
干预措施: Placebo (Drug)
Cohort B: 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.
干预措施: Placebo (Drug)
Cohort B: 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.
干预措施: Maridebart Cafraglutide (Biological)
Cohort B: 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.
干预措施: Maridebart Cafraglutide (Biological)
Cohort A: 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.
干预措施: Maridebart Cafraglutide (Biological)
Cohort A: 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.
干预措施: Maridebart Cafraglutide (Biological)
结局指标
主要结局
Percent Change From Baseline to Week 52 in Body Weight
时间窗: Baseline and Week 52
次要结局
- Percentage of Participants Achieving ≥ 10% Reduction in Body Weight From Baseline at Week 52(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 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)
- 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)
- 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)
- Change from Baseline to Week 52 in Lean Body Mass Using DEXA(Baseline and Week 52)
- 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)