Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese

A Randomized, Double-Blind, Placebo-Controlled Multi-Center Study of Intravenous Bimagrumab, Alone or in Addition to Open Label Subcutaneous Semaglutide, to Investigate the Efficacy and Safety in Overweight or Obese Men and Women

A phase 2 study to assess the efficacy of bimagrumab alone or in addition to semaglutide to assess efficacy and safety in overweight or obese men and women

Study Overview

• Status: Completed
• Conditions: Obesity; Obese; Overweight or Obesity
• Intervention / Treatment: Other: Placebo; Drug: Semaglutide; Biological: Bimagrumab

Detailed Description

This study investigates if bimagrumab in addition to semaglutide is able to preserve/increase muscle mass in the presence of weight and/or fat mass loss.

• Study Type: Interventional
• Enrollment (Actual): 507
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Camberwell, Australia, 3124
    • Emeritus Research
  • New South Wales
    • Brookvale, New South Wales, Australia, 2100
      • Northern Beaches Clinical Research
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Morayfield, Queensland, Australia, 4506
      • University of The Sunshine Coast Morayfield
    • Sippy Downs, Queensland, Australia, 04556
      • University of the Sunshine Coast Clinical Trial Centre
    • South Brisbane, Queensland, Australia, 4101
      • University of The Sunshine Coast South Brisbane
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • Victoria
    • Heidelberg Heights, Victoria, Australia, 3081
      • Austin Health
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Hospital
  • Auckland, New Zealand, 1010
    • Optimal Clinical Trials
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research Auckland
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research Christchurch
  • Hamilton, New Zealand, 3200
    • Lakeland Clinical Trials Waikato
  • Nelson, New Zealand, 7011
    • Southern Clinical Trials Tasman
  • Canterbury
    • Beckenham, Christchurch, Canterbury, New Zealand, 8013
      • Southern Clinical Trials Ltd
  • Wellington Region
    • Newtown, Wellington Region, New Zealand, 6242
      • P3 Research
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Cullman, Alabama, United States, 35055
      • Cullman Clinical Trials
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc
    • Lake Worth, Florida, United States, 33461
      • Altus Research
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
  • South Carolina
    • Columbia, South Carolina, United States, 29322
      • SPICA Clinical
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Mt. Olympus Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• A written informed consent must be obtained before any study-related assessments are performed.

• Men and women between 18 and 80 years, inclusive; women of child-bearing potential (defined as those who are not post-menopausal or post-surgical sterilization) must meet both of the following criteria:

  • Two negative pregnancy tests (at screening and at randomization, prior to dosing)
  • Use of intrauterine device, from at least 3 months before the baseline visit through at least 4 months after the last dose of bimagrumab/placebo i.v., and an additional contraceptive (barrier) method from screening through at least 4 months after the last dose of bimagrumab/placebo i.v.
• Body mass index (BMI) ≥ 30 or BMI ≥ 27 with one or more obesity-associated comorbidities (e.g., hypertension, insulin resistance, sleep apnea, or dyslipidemia)
• Stable body weight (± 5 kg) within 90 days of screening, and body weight <150 kg
• Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
• Able to communicate well with the Investigator, comply with the study requirements and adhere to the diet and activity programs for the study duration

Key Exclusion Criteria:

• History of, or known hypersensitivity to, monoclonal antibody drugs or a contraindication to semaglutide (Ozempic® or Wegovy®)
• Use of other investigational drugs at the time of enrollment or within 30 days or 5 half-lives of enrollment, whichever is longer, or longer if required by local regulations
• Treatment with any medication for the indication of obesity within the past 30 days before screening
• Diagnosis of diabetes requiring current use of any antidiabetic drug or HbA1c ≥ 6.5% Note: Metabolic syndrome is not an exclusion, even if managed with an anti-diabetic drug such as metformin or an SGLT2 inhibitor. A diagnosis of prediabetes or impaired glucose tolerance managed exclusively with non-pharmacologic approaches (e.g., diet and exercise) is not an exclusion.
• Any chronic infections likely to interfere with study conduct or interpretation such as hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). History of hepatitis A or hepatitis C successfully treated is not exclusionary. Active COVID-19 infection.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation, or plasma donation (> 250 mL) within 14 days prior to the first dose
• Any disorder, unwillingness, or inability not covered by any of the other exclusion criteria, which in the Investigator's opinion, might jeopardize the participant's safety or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo/30 mg/kg Bimagrumab; Participants received intravenous placebo at baseline and at Weeks 4, 16, 28, and 40, followed by intravenous 30 milligrams per kilogram (mg/kg) bimagrumab at Weeks 52 and 64.	Other: Placebo; Placebo
Experimental: 10/30 mg/kg Bimagrumab; Participants received intravenous 10 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, and 40, followed by intravenous 30 mg/kg bimagrumab at Weeks 52 and 64.	Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
Experimental: 30 mg/kg Bimagrumab; Participants received intravenous 30 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, 40, 52, and 64.	Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
Experimental: Placebo + 1.0 mg Semaglutide; Participants received intravenous placebo at baseline and at Weeks 4, 16, 28, 40 and subcutaneous 1.0 milligram (mg) semaglutide weekly as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 71: 1.0 mg	Other: Placebo; Placebo; Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy
Experimental: Placebo + 2.4 mg Semaglutide; Participants received intravenous placebo at baseline and at Weeks 4, 16, 28, 40 and subcutaneous 2.4 mg semaglutide weekly per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 12: 1.0 mg; Weeks 13 to 16: 1.7 mg; Weeks 17 to 71: 2.4 mg	Other: Placebo; Placebo; Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy
Experimental: 10 mg/kg Bimagrumab + 1.0 mg Semaglutide; Participants received intravenous 10 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, 40, 52, and 64, and subcutaneous 1.0 mg semaglutide weekly as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 71: 1.0 mg	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy; Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
Experimental: 10 mg/kg Bimagrumab + 2.4 mg Semaglutide; Participants received intravenous 10 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, 40, 52, and 64, and subcutaneous 2.4 mg semaglutide weekly as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 12: 1.0 mg; Weeks 13 to 16: 1.7 mg; Weeks 17 to 71: 2.4 mg	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy; Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
Experimental: 30 mg/kg Bimagrumab + 1.0 mg Semaglutide; Participants received intravenous 30 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, 40, 52, and 64, and subcutaneous 1.0 mg semaglutide weekly as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 71: 1.0 mg	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy; Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
Experimental: 30 mg/kg Bimagrumab + 2.4 mg Semaglutide; Participants received intravenous 30 mg/kg bimagrumab at baseline and at Weeks 4, 16, 28, 40, 52, and 64, and subcutaneous 2.4 mg semaglutide weekly as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg; Weeks 5 to 8: 0.5 mg; Weeks 9 to 12: 1.0 mg; Weeks 13 to 16: 1.7 mg; Weeks 17 to 71: 2.4 mg	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Ozempic; Wegovy; Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Body Weight at Week 48	Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Body Mass Index (BMI) Categories at Baseline and Week 48	BMI categories: i. Healthy weight: 18.5 kilograms (kg)/meter (m)² to 24.9 kg/m² ii. Overweight: 25 kg/m² to 29.9 kg/m² iii. Obesity class 1: 30 kg/m² to 34.9 kg/m² iv. Obesity class II: 35 kg/m² to 39.9 kg/m² v. Obesity class III: ≥ 40 kg/m2	Baseline, Week 48
Percentage of Participants With Baseline Waist-to-Height Ratio (WtHR) Category of <0.5 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48	WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6	Baseline up to 48 weeks
Percentage of Participants With Baseline WtHR Category of 0.5-0.59 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48	WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6	Baseline up to 48 weeks
Percentage of Participants With Baseline WtHR Category ≥0.6 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48	WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6	Baseline up to 48 weeks
Change From Baseline in Quality of Life Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 24	The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores.	Baseline, Week 24
Change From Baseline in Quality of Life SF-36v2 Acute Form Physical Functioning Domain Score Week 48	The SF-36v2 acute form assesses HRQoL on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10 items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores	Baseline, Week 48
Change From Baseline in Quality of Life SF-36v2 Acute Form Total Score at Week 48	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into MCS and PCS to obtain a total score ranging from 0 to 100, with higher scores indicating better levels of function and/or better health.	Baseline, Week 48
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Score and Total Score at Week 24	The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'	Baseline, Week 24
Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 48	The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'	Baseline, Week 48
Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 72	The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'	Baseline, Week 72
Change From Baseline in Waist Circumference at Week 48	Waist circumference was measured in standing position with a non-stretchable measuring tape to the nearest 0.1 centimeter (cm). Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Change From Baseline in Waist Circumference at Week 72	Waist circumference was measured in standing position with a non-stretchable measuring tape to the nearest 0.1 cm. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Change From Baseline in Total Body Fat Mass in Kilograms (kg) at Week 48	Change from baseline in total body fat mass in kg was assessed by Dual energy X-ray absorptiometry (DXA). Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Change From Baseline in Total Body Fat Mass in kg at Week 72	Change from baseline in total body fat mass in kg was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Percent Change From Baseline for Fat Mass by DXA at Week 48	Percent change from baseline for fat mass was assessed by DXA. Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Percent Change From Baseline for Fat Mass by DXA at Week 72	Percent change from baseline for fat mass was assessed by DXA. Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Change From Baseline in Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Trunk Fat Mass by DXA at Week 48	Change from baseline in VAT, SAT and trunk fat mass was assessed by DXA. Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Change From Baseline in VAT, SAT and Trunk Fat Mass by DXA at Week 72	Change from baseline in VAT, SAT and trunk fat mass was assessed by DXA. Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Percentage of Participants With Reduction in Waist Circumference Greater Than or Equal to (≥) 5 cm at Week 48	Waist circumference was measured in a standing position with a non-stretchable measuring tape to the nearest 0.1 cm. Only participants with non-missing baseline value were included in analysis.	Week 48
Percentage of Participants With Reduction in Body Weight ≥ 5%, ≥ 10% and ≥15% at Week 48	Body weight was measured in kgs to the nearest 0.1 kg. Only participants with non-missing baseline value were included in analysis.	Week 48
Percentage of Participants With Reduction in Fat Mass ≥ 5% ≥ 10% ≥ 15% by DXA at Week 48	Only participants with non-missing baseline value were included in analysis.	Week 48
Percentage of Participants Achieving Fat Mass ≥ 10% Reduction With <5% Decrease in Lean Mass by DXA at Week 48	Only participants with non-missing baseline value were included in analysis.	Week 48
Percentage of Participants Achieving >5 kg Weight Loss and Fat Loss Index (FLI) of >70%, >80%, and >90% by DXA at Week 48	Fat Lost Index = % change in fat mass/% change in lean mass + % change in fat mass. Only participants with non-missing baseline value were included in analysis.	Week 48
Change From Baseline in Body Fat Mass by Bioelectrical Impedance Analysis (BIA) at Week 48	Change from baseline in body fat mass was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 48
Change From Baseline in Body Fat Mass by BIA at Week 72	Change from baseline in body fat mass was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 72
Percent Change From Baseline in Body Fat by BIA at Week 48	Percent change from baseline in Body fat was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 48
Percent Change From Baseline in Body Fat by BIA at Week 72	Percent change from baseline in Body fat was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 72
Change From Baseline in Lean Mass by DXA at Week 48	Change from baseline in lean mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Change From Baseline in Lean Mass by DXA at Week 72	Change from baseline in lean mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Percent Change From Baseline in Lean Body Mass by DXA at Week 48	Percent change from baseline in lean body mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Percent Change From Baseline in Lean Body Mass by DXA at Week 72	Percent change from baseline in lean body mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Percent Change From Baseline in Appendicular Lean Mass by DXA at Week 48	Percent change from baseline in appendicular lean mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 48
Percent Change From Baseline in Appendicular Lean Mass by DXA at Week 72	Percent change from baseline in appendicular lean mass was assessed by DXA. Least Square mean was determined by mixed model repeated measures (MMRM) model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, Week 72
Change From Baseline in Lean Mass (kg) by BIA at Week 48	Change from baseline in lean mass (kg) was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 48
Change From Baseline in Lean Mass (kg) by BIA at Week 72	Change from baseline in lean mass (kg) was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 72
Percent Change From Baseline in Lean Body Mass by BIA at Week 48	Percent change from baseline in lean body mass was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 48
Percent Change From Baseline in Lean Body Mass by BIA at Week 72	Percent change from baseline in lean body mass was assessed through BIA. LS mean was determined using MMRM model for post-baseline measures: Variable is modelled by Treatment, Visit, Treatment-by-Visit interaction, Sex, and Country as fixed effects, with Baseline as a covariate. Variance-Covariance structure = Unstructured. Only participants with non-missing baseline value were included in the analysis.	Baseline, Week 72
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 48	HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Square mean was determined by MMRM model for post-baseline measures: Variable is modelled by Gender (Male, Female), Country (Australia, New Zealand, United States of America), Visit, Treatment, and Visit-by-Treatment interaction as fixed effects, and Baseline as a covariate. Variance-Covariance structure= Unstructured. Only participants with non-missing baseline value were included in analysis. No imputation was performed for missing values.	Baseline, 48 weeks
Change From Baseline in Quality of Life SF-36v2 Acute Form Total Score Week 24	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into (mental component score [MCS] and physical component score [PCS] to obtain a total score ranging from 0 to 100, with higher scores indicating better levels of function and/or better health.	Baseline, Week 24
Change From Baseline in Quality of Life SF-36v2 Acute Form Physical Functioning Domain Score Week 72	The SF-36v2 acute form assesses HRQoL on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10 items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores	Baseline, Week 72
Change From Baseline in Quality of Life SF-36v2 Acute Form Total Score at Week 72	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into MCS and PCS to obtain a total score ranging from 0 to 100, with higher scores indicating better levels of function and/or better health.	Baseline, Week 72

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Versanis Bio, Inc.
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Heymsfield SB, Aronne LJ, Montgomery P, Klickstein LB, Coleman LA, Dole K, Mindeholm L, Spruill S, Li X, Attie KM; BELIEVE trial investigators. Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial. Nat Med. 2026 Mar;32(3):869-882. doi: 10.1038/s41591-026-04204-0. Epub 2026 Mar 2.
• Moon S, Choi JW, Park JH, Kim DS, Ahn Y, Kim Y, Kong SH, Oh CM. Association of Appendicular Skeletal Muscle Mass Index and Insulin Resistance With Mortality in Multi-Nationwide Cohorts. J Cachexia Sarcopenia Muscle. 2025 Apr;16(2):e13811. doi: 10.1002/jcsm.13811.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2022
• Primary Completion (Actual): May 16, 2024
• Study Completion (Actual): June 14, 2025

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: November 9, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: semaglutide; bimagrumab
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide; bimagrumab
• Other Study ID Numbers: 18828; VER201-PH2-031 (Other Identifier: Versanis); J4Z-MC-GIDA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No