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

Amgen

Status and phase: Active, not recruiting; Phase 2

Conditions: Overweight; Type 2 Diabetes Mellitus; Obesity

Treatments: Drug: Placebo; Biological: Maridebart Cafraglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05669599

20190218

Details and patient eligibility

About

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).

Enrollment: 592 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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592 participants in 4 patient groups, including a placebo group

Cohort A: Maridebart Cafraglutide

Experimental group

Description:

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.

Treatment:

Biological: Maridebart Cafraglutide

Drug: Placebo

Cohort A: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Biological: Maridebart Cafraglutide

Drug: Placebo

Cohort B: Maridebart Cafraglutide

Experimental group

Description:

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.

Treatment:

Biological: Maridebart Cafraglutide

Drug: Placebo

Cohort B: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Biological: Maridebart Cafraglutide

Drug: Placebo