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Efficacy and Safety of Maridebart Cafraglutide in Adult Participants in Japan Who Have Obesity Disease

Phase 3
Not yet recruiting
Conditions
Obesity Disease
Interventions
Registration Number
NCT06987695
Lead Sponsor
Amgen
Brief Summary

The primary objective of this study is to demonstrate that maridebart cafraglutide is superior to placebo for percent change in body weight and proportion of participants with ≥ 5% reduction in body weight.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
272
Inclusion Criteria
  • Age ≥ 18 years.

  • History of at least 1 self-reported unsuccessful attempt at weight loss by diet and exercise.

  • Body mass index (BMI) ≥ 35 kg/m^2 at screening with a current diagnosis of at least 1 of the weigh-related comorbidities specified in the Japan Society for the Study of Obesity (JASSO) guideline OR BMI ≥ 27 kg/m^2 to < 35 kg/m^2 at screening, with a current diagnosis of at least 2 of the weight-related comorbidities specified in the JASSO guideline.

  • For both BMI categories, at least 1 of the weight-related comorbidities must be hypertension, dyslipidemia, or T2DM.

    1. hypertension: treated, or with SBP ≥ 140 mmHg, or DBP ≥ 90 mmHg at screening.
    2. dyslipidemia: treated, or with LDL > 140 mg/dL (3.6 mmol/L), or triglycerides ≥ 150 mg/dL (1.7 mmol/L), non-HDL cholesterol > 170 mg/dL (4.4 mmol/L) or HDL < 40 mg/dL (1.0 mmol/L) at screening.
    3. T2DM: diagnosed ≥ 180 days before screening, and treated with diet and exercise alone and/or a stable treatment for at least 90 days before screening with up to 3 oral glucose-lowering medications (as per local labeling) (except for glucagon-like peptide-1 receptor agonists [GLP-1RA] and dipeptidyl peptidase-4 [DPP-4] inhibitors), and have a HbA1c ≥ 7% and ≤ 10% (53-86 mmol/mol) at screening.
  • In the opinion of the investigator, well-motivated and willing to:

    1. Follow study procedures for the duration of the study, including, but not limited to, follow lifestyle advice, maintain a study log(s)/diary(ies), and complete required study visits and questionnaires.
    2. Perform self-monitoring blood glucose (SMBG) per protocol (only for participants with T2DM).
Exclusion Criteria
  • Obesity induced by other endocrinological disorders or monogenetic or syndromic forms of obesity.
  • Self-reported change in body weight > 5 kg within 90 days before screening.
  • Previous or planned (during the study) surgical, endoscopic, or device-based treatment for obesity.
  • For participants without diabetes at screening, type 1 or 2 diabetes mellitus or any other types of diabetes mellitus (except history of gestational diabetes).
  • For participants with T2DM at screening, any other type(s) of diabetes, mellitus except T2DM.
  • History of chronic pancreatitis or history of acute pancreatitis within 180 days before screening.
  • Family (first-degree relative[s]) or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2).
  • History of unstable major depressive disorder (MDD) or other severe psychiatric disorder within 2 years before screening.
  • Lifetime history of suicide attempt.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Maridebart Cafraglutide High DoseMaridebart cafraglutideParticipants will receive maridebart cafraglutide high dose subcutaneously (SC) for 72 weeks.
Maridebart Cafraglutide Medium DoseMaridebart cafraglutideParticipants will receive maridebart cafraglutide medium dose SC for 72 weeks.
Maridebart Cafraglutide Low DoseMaridebart cafraglutideParticipants will receive maridebart cafraglutide low dose SC for 72 weeks.
PlaceboPlaceboParticipants will receive placebo SC for 72 weeks.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Body Weight at Week 72Baseline and Week 72
Participants Achieving ≥ 5% Reduction in Body Weight From Baseline at Week 72Baseline and Week 72
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Waist Circumference at Week 72Baseline and Week 72
Participants Achieving ≥ 10% Reduction in Body Weight from Baseline at Week 72Baseline and Week 72
Participants Achieving ≥ 15% Reduction in Body Weight from Baseline at Week 72Baseline and Week 72
Change From Baseline in Body Weight at Week 72Baseline and Week 72
Percent Change From Baseline in Body Weight in Participants Without Type 2 Diabetes Mellitus (T2DM) at Week 72Baseline and Week 72
Percent Change From Baseline in Body Weight in Participants With T2DM at Week 72Baseline and Week 72
Change From Baseline in Body Mass Index (BMI) at Week 72Baseline and Week 72
Participants Achieving ≥ 20% Reduction in Body Weight from Baseline at Week 72Baseline and Week 72
Change From Baseline in Visceral Fat Area (VFA) at Week 72Baseline and Week 72
Participants Achieving VFA < 100 cm^2 in VFA at Week 72Week 72
Percent Change From Baseline in Fasting Total Cholesterol at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (non-HDL-C) at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting Triglycerides at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting High-density Lipoprotein Cholesterol (HDL-C) at Week 72Baseline and Week 72
Change From Baseline in Systolic Blood Pressure (SBP) at Week 72Baseline and Week 72
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 72Baseline and Week 72
Change From Baseline in Fasting Plasma Glucose at Week 72Baseline and Week 72
Percent Change From Baseline in Fasting Insulin at Week 72Baseline and Week 72
Change from Baseline in Hemoglobin A1c (HbA1c) at Week 72Baseline and Week 72
Percentage of Participants with a Change from Baseline in Glycemic Status at Week 72 for Participants Without T2DM at BaselineBaseline and Week 72

Glycemic status was categorized as:

* normoglycemic (fasting plasma glucose \< 100 mg/dL and HbA1c \< 5.7%, in absence of T2DM diagnosis),

* prediabetes (fasting plasma glucose 100 - 125 mg/dL or HbA1c 5.7% - 6.4% in the absence of a T2DM diagnosis),

* or, T2DM (fasting plasma glucose ≥ 126 mg/dL and HbA1c ≥6.5%).

Participants With T2DM Achieving HbA1c < 7% at Week 72Week 72
Participants With T2DM Achieving HbA1c ≤ 6.5% at Week 72Week 72
Participants With T2DM Achieving HbA1c < 5.7% at Week 72Week 72
Change From Baseline in Short Form 36 Health Survey Version 2 (SF-36v2) Acute Physical Function Domain Score at Week 72Baseline and Week 72

The SF-36v2 Acute Physical Function domain score measures an individual's ability to perform daily physical activities, such as walking and climbing stairs, over the past week. It includes 10 items scored on a 3-point Likert scale, with raw scores transformed to a 0-100 scale. Higher scores indicate better physical functioning and fewer limitations due to physical health.

Change from Baseline in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72Baseline and Week 72

The IWQOL-Lite-CT is a 20-item questionnaire designed to assess the impact of weight on quality of life in clinical trials. Items are scored on a 5-point Likert scale, with raw scores transformed to a 0-100 scale, where higher scores indicate better quality of life and less weight-related impact.

Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)Up to Week 84
Number of Participants Experiencing Serious Adverse EventsUp to Week 84
Plasma Concentration of Maridebart Cafraglutide at Week 72Week 72
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