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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Obesity, Obese, Overweight or Obesity

Intervention / Treatment
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* Biological: Bimagrumab
* Drug: Semaglutide
* Other: Bimagrumab Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The study is designed to have three periods. The 48-week core treatment period has 9 treatment arms, with combinations of 3 semaglutide doses (none, 1.0 mg and 2.4 mg) and 3 bimagrumab doses (0, 10 and 30 mg/kg). The core treatment period is then followed by an open-label 24-week treatment extension period during which participants originally assigned to either placebo or bimagrumab 10 mg/kg will switch to bimagrumab 30 mg/kg. All other treatment assignments will remain the same. The extension period is then followed by a 32-week post-treatment period, during which all study treatments will be withdrawn from all arms.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo to bimagrumab 30 mg/kg + no semaglutide<br>Participants will receive i.v. placebo at baseline and at Weeks 4, 16, 28 and 40 during the core treatment period and will switch during the extension period to receive bimagrumab 30 mg/kg at Weeks 52 and 64. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>Other: Bimagrumab Placebo<br>* Placebo<br>|
| Other: Placebo + semaglutide 1.0 mg<br>Participants will receive i.v. placebo at baseline and at Weeks 4, 16, 28, 40, 52 and 64, and s.c. semaglutide 1.0 mg weekly per the dose escalation schedule. | Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;Other: Bimagrumab Placebo<br>* Placebo<br>|
| Other: Placebo + semaglutide 2.4 mg<br>Participants will receive i.v. placebo at baseline and at Weeks 4, 16, 28 and 40, 52 and 64, and s.c. semaglutide 2.4 mg weekly per the dose escalation schedule. | Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;Other: Bimagrumab Placebo<br>* Placebo<br>|
| Experimental: Bimagrumab 10 mg/kg to bimagrumab 30 mg/kg + no semaglutide<br>Participants will receive i.v. bimagrumab 10 mg/kg at baseline and at Weeks 4, 16, 28 and 40 during the core treatment period and will switch during the extension period to receive bimagrumab 30 mg/kg at Weeks 52 and 64. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>|
| Other: Bimagrumab 10 mg/kg + semaglutide 1.0 mg<br>Participants will receive i.v. bimagrumab 10 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64, and s.c. semaglutide 1.0 mg weekly per the dose escalation schedule. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;|
| Other: Bimagrumab 10 mg/kg + semaglutide 2.4 mg<br>Participants will receive i.v. bimagrumab 10 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64, and s.c. semaglutide 2.4 mg weekly per the dose escalation schedule. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;|
| Experimental: Bimagrumab 30 mg/kg + no semaglutide<br>Participants will receive i.v. bimagrumab 30 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>|
| Other: Bimagrumab 30 mg/kg + semaglutide 1.0 mg<br>Participants will receive i.v. bimagrumab 30 mg/kg at baseline, and at Weeks 4, 16, 28, 40, 52 and 64, and s.c. semaglutide 1.0 mg weekly per the dose escalation schedule. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;|
| Other: Bimagrumab 30 mg/kg + semaglutide 2.4 mg<br>Participants will receive i.v. bimagrumab 30 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64, and s.c. semaglutide 2.4 mg per the dose escalation schedule. | Biological: Bimagrumab<br>* Human monoclonal antibody to the activin receptor type II<br>Drug: Semaglutide<br>* Glucagon-like peptide-1 (GLP-1) receptor agonist<br>* Other names: Ozempic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in body weight at 48 weeks | Change in total body weight will be measured from baseline to 48 weeks | At baseline and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in waist circumference (cm) at 48 weeks | Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm). | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in total body fat mass in kilograms (kg) | Fat mass will be obtained by dual-energy x-ray absorptiometry (DXA) Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in percent body fat | Percent body fat will be obtained by dual-energy x-ray absorptiometry (DXA) Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and trunk fat mass by dual-energy x-ray absorptiometry (DXA) | Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline and 48 weeks | 
| Proportion of participants at 48 weeks with change in waist circumference ≥ 5 cm | Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm). | At baseline and 48 weeks | 
| Proportion of participants at 48 weeks with change in Body weight ≥ 5%, ≥ 10% and ≥15% | Body weight will be measured in kilograms (kg) to the nearest 0.1 kg. | At baseline and 48 weeks | 
| Proportion of participants at 48 weeks with change in Fat mass ≥ 5% ≥ 10% ≥ 15% by Dual energy X-ray absorptiometry (DXA) | Dual energy X-ray absorptiometry (DXA) will be used to assess the changes in body composition. | At baseline and 48 weeks | 
| Proportion of participants at 48 weeks with change in Fat mass ≥ 10% with <5% decrease (or and increase) in lean mass by Dual energy X-ray absorptiometry (DXA) | Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline and 48 weeks | 
| Percentage of weight loss due to fat mass or lean mass at 48 weeks by dual-energy x-ray absorptiometry (DXA) | Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in fat mass (kg and %) by bioelectrical impedance analysis (BIA) | Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition. | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in lean mass (kg and %) and appendicular lean mass by dual-energy x-ray absorptiometry (DXA) | Dual-energy x-ray absorptiometry (DXA) will be used to assess changes in body composition. | At baseline 48 weeks | 
| Change from baseline at 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA) | Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition. | At baseline 48 weeks | 
| Safety and tolerability measurements throughout 48 weeks by TEAEs [safety labs, vital signs] | Incidence and severity of treatment emergent adverse events (TEAEs) | Baseline and 48 weeks | 
| Proportion of Participants with change from baseline in Body Mass Index (BMI) categories at 48 weeks | BMI categories: i. Healthy weight: 18.5 kg/m2 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 | At baseline and 48 weeks | 
| Proportion of Participants with change from baseline in waist-to-height ratio (WHtR ratio) categories at 48 weeks | WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6 | At baseline and 48 weeks | 
| Change from baseline in HbA1c (mmol/mol) at 48 weeks | To assess treatment effects on glucose metabolism and HbA1c. | At baseline and 48 weeks | 
| Change from baseline at 48 weeks in Quality of Life Short Form 36 (SF-36) survey | Change from baseline at 48 weeks in Quality of Life Short Form 36 (SF-36) survey. To assess a subject's overall health related quality of life, as well as the physical functioning score. SF- 36 scores range from 0 (worst) to 100 (best) | At baseline and 48 weeks | 
| Change from Baseline at 48 weeks in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite) | Change from baseline in IWQOL-Lite CT. IWQOL-Lite CT is a 20-item modified survey instrument that is used to quantitatively assess an individual's perception of how their weight affects their day- to-day life, as well as the physical function score. Scores range from 0 (worst) to 100 (best) | At baseline and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bimagrumab, semaglutide