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

Eli Lilly and Company507 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

507

Conditions

Obesity Obese Overweight or Obesity

Interventions

BimagrumabBIOLOGICAL

Human monoclonal antibody to the activin receptor type II

SemaglutideDRUG

Glucagon-like peptide-1 (GLP-1) receptor agonist

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (26)

Pinnacle Research Group, LLC

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Week 48

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline, Week 72

Change From Baseline in Total Body Fat Mass in Kilograms (kg) at Week 48

Data from ClinicalTrials.gov

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Anniston, Alabama, United States

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Cullman, Alabama, United States

Indago Research & Health Center, Inc

Hialeah, Florida, United States

Clinical Neuroscience Solutions Inc

Jacksonville, Florida, United States

Altus Research

Lake Worth, Florida, United States

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Weill Cornell Medical College

New York, New York, United States

Monroe Biomedical Research

Monroe, North Carolina, United States

SPICA Clinical

Columbia, South Carolina, United States

Mt. Olympus Medical Research

Sugar Land, Texas, United States

...and 16 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 48

Percent Change From Baseline for Fat Mass by DXA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Change From Baseline in VAT, SAT and Trunk Fat Mass by DXA at Week 72

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 48

Change From Baseline in Body Fat Mass by BIA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Percent Change From Baseline in Body Fat by BIA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Change From Baseline in Lean Mass by DXA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Percent Change From Baseline in Lean Body Mass by DXA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Percent Change From Baseline in Appendicular Lean Mass by DXA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Change From Baseline in Lean Mass (kg) by BIA at Week 72

Time frame: 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.

Time frame: Baseline, Week 48

Percent Change From Baseline in Lean Body Mass by BIA at Week 72

Time frame: Baseline, Week 72

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline up to 48 weeks

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.

Time frame: Baseline, 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.

Time frame: Baseline, Week 24

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.

Time frame: 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

Time frame: 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.

Time frame: Baseline, Week 48

Change From Baseline in Quality of Life SF-36v2 Acute Form Physical Functioning Domain Score Week 72

Time frame: 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.

Time frame: Baseline, Week 72

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.'

Time frame: Baseline, Week 24

Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 48

Time frame: Baseline, Week 48

Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 72

Time frame: Baseline, Week 72