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

• ClinicalTrials.gov Identifier: NCT05616013
• Recruitment Status: Active, not recruiting
• First Posted: November 14, 2022
• Last Update Posted: February 1, 2024
• Sponsor: Eli Lilly and Company
• Collaborator: Versanis Bio, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 16, 2022
• First Posted Date: November 14, 2022
• Last Update Posted Date: February 1, 2024
• Actual Study Start Date: November 16, 2022
• Estimated Primary Completion Date: May 20, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2023)

Change from baseline in body weight at 48 weeks [ Time Frame: At baseline and 48 weeks ]

Change in total body weight will be measured from baseline to 48 weeks

Original Primary Outcome Measures (submitted: November 9, 2022)

Change from baseline in WC (cm) at 48 weeks [ Time Frame: At baseline and 48 weeks ]

Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).

Current Secondary Outcome Measures (submitted: November 9, 2023)

• Change from baseline in waist circumference (cm) at 48 weeks [ Time Frame: At baseline and 48 weeks ]
  Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).
• Change from baseline at 48 weeks in total body fat mass in kilograms (kg) [ Time Frame: At baseline and 48 weeks ]
  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.
• Change from baseline at 48 weeks in percent body fat [ Time Frame: At baseline and 48 weeks ]
  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.
• 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) [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Proportion of participants at 48 weeks with change in waist circumference ≥ 5 cm [ Time Frame: At baseline and 48 weeks ]
  Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).
• Proportion of participants at 48 weeks with change in Body weight ≥ 5%, ≥ 10% and ≥15% [ Time Frame: At baseline and 48 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Proportion of participants at 48 weeks with change in Fat mass ≥ 5% ≥ 10% ≥ 15% by Dual energy X-ray absorptiometry (DXA) [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess the changes in body composition.
• 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) [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Percentage of weight loss due to fat mass or lean mass at 48 weeks by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Change from baseline at 48 weeks in fat mass (kg and %) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline and 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition.
• Change from baseline at 48 weeks in lean mass (kg and %) and appendicular lean mass by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline 48 weeks ]
  Dual-energy x-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Change from baseline at 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition.
• Safety and tolerability measurements throughout 48 weeks by TEAEs [safety labs, vital signs] [ Time Frame: Baseline and 48 weeks ]
  Incidence and severity of treatment emergent adverse events (TEAEs)
• Proportion of Participants with change from baseline in Body Mass Index (BMI) categories at 48 weeks [ Time Frame: At baseline and 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
• Proportion of Participants with change from baseline in waist-to-height ratio (WHtR ratio) categories at 48 weeks [ Time Frame: At baseline and 48 weeks ]
  WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6
• Change from baseline in HbA1c (mmol/mol) at 48 weeks [ Time Frame: At baseline and 48 weeks ]
  To assess treatment effects on glucose metabolism and HbA1c.
• Change from baseline at 48 weeks in Quality of Life Short Form 36 (SF-36) survey [ Time Frame: At baseline and 48 weeks ]
  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)
• Change from Baseline at 48 weeks in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite) [ Time Frame: At baseline and 48 weeks ]
  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)

Original Secondary Outcome Measures (submitted: November 9, 2022)

• Change from baseline in WC (cm) at 24 weeks [ Time Frame: At baseline and 24 weeks ]
  Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).
• Change from baseline in total body weight in kilograms (kg) at 24 weeks and 48 weeks [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Percent change from baseline in total body weight in kilograms (kg) at 24 weeks and 48 weeks [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg and reported as a percentage.
• Change from baseline to 24 weeks and 48 weeks in lean mass (kg) by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Percent change from baseline to 24 weeks and 48 weeks in lean mass (percent body lean) by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Change from baseline to 24 weeks and 48 weeks in fat mass (kg) by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Percent change from baseline to 24 weeks and 48 weeks in fat mass (percent body fat) by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Change from baseline to 24 weeks and 48 weeks in Visceral Adipose Tissue(VAT)/trunk fat mass (kg) by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
• Percent change from baseline to 24 weeks and 48 weeks in Visceral Adipose Tissue(VAT)/trunk fat mass by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition. Changes will be reported in percentage.
• Change from baseline at 24 weeks and 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition and will be used to assess lean mass (kg)
• Percent change from baseline at 24 weeks and 48 weeks in lean mass (percent lean mass) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline, 24 weeks and 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition and will be used to assess percent change in lean mass.
• Change from baseline to 24 weeks and 48 weeks in fat mass (kg) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline, 24 weeks, 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition. An estimate of total body water (TBW) is derived by measuring electrical impedance of body tissues, from which fat-free mass (FFM) and body fat (adiposity) are estimated.
• Percent change from baseline to 24 weeks and 48 weeks in fat mass (percent body fat) by bioelectrical impedance analysis (BIA) [ Time Frame: At baseline, 24 weeks, 48 weeks ]
  Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition. An estimate of total body water (TBW) is derived by measuring electrical impedance of body tissues, from which fat-free mass (FFM) and body fat (adiposity) are estimated.
• Proportion of participants at 24 weeks with change in waist circumference ≥ 5 cm [ Time Frame: At baseline and 24 weeks ]
  Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).
• Proportion of participants at 48 weeks with change in waist circumference ≥ 5 cm [ Time Frame: At baseline and 48 weeks ]
  Waist circumference will be measured in standing position with a non-stretchable measuring tape and to the nearest 0.1 centimeter (cm).
• Proportion of participants at 24 weeks with change in Body weight ≥ 5% and ≥ 10% [ Time Frame: At baseline and 24 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Proportion of participants at 48 weeks with change in Body weight ≥ 5% and ≥ 10% [ Time Frame: At baseline and 48 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Proportion of participants at 48 weeks with change in Fat mass ≥ 5% and ≥ 10% [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess the change in fat mass.
• Proportion of participants at 24 weeks with change in fat mass ≥ 5% and ≥ 10% [ Time Frame: At baseline and 24 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess the change in fat mass.
• Proportion of participants at 24 weeks with change in Fat mass ≥ 10% with <5% decrease (or increase) in lean mass [ Time Frame: At baseline and 24 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess body composition.
• Proportion of participants at 48 weeks with change in Fat mass ≥ 10% with <5% decrease (or increase) in lean mass [ Time Frame: At baseline and 48 weeks ]
  Dual energy X-ray absorptiometry (DXA) will be used to assess body composition.
• Percentage of weight loss (kg) due to fat mass or lean mass at 24 weeks [ Time Frame: At baseline and 24 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Percentage of weight loss (kg) due to fat mass or lean mass at 48 weeks [ Time Frame: At baseline and 48 weeks ]
  Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
• Safety and tolerability measurements throughout 48 weeks by TEAEs [ Time Frame: Baseline and 48 weeks ]
  Incidence and severity of treatment emergent adverse events (TEAEs)
• Proportion of patients with change from baseline in BMI categories at 24 weeks and 48 weeks [ Time Frame: At baseline, 24 weeks, and 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 34.9 kg/m2 v. Obesity class III: ≥ 40 kg/m2
• Proportion of patients with change from baseline in WHtR ratio categories at 24 weeks and 48 weeks [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6
• To assess treatment effects on glucose metabolism in HbA1c [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Change from baseline in HbA1c (mmol/mol) at 24 and 48 weeks.
• To assess treatment effects on glucose metabolism in Homeostasis Model Assessment version 2 (HOMA2) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Change from baseline in HOMA2 at 24 and 48 weeks. Calculations reporting steady state beta cell function (%B) and Insulin sensitivity (%S)
• To assess treatment effects on glucose metabolism in the Quantitative Insulin Sensitivity Check Index (QUICKI) [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Change from baseline in QUICKI at 24 and 48 weeks. QUICKI is an index to assess fasting blood glucose and insulin levels. Greater than 0.45: Normal reference level; 0.30 - 0.45: Insulin resistance likely; Less than 0.339: Associated with a trend towards insulin resistance; Less than 0.30: Diabetes diagnosis likely
• To assess treatment effects on self-reported health status quality of life [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  Change from baseline to 24 weeks and 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)
• To assess treatment effects on self-reported weight-related quality of life [ Time Frame: At baseline, 24 weeks, and 48 weeks ]
  The Impact of Weight on Quality of Life-Lite for Clinical Trials (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. Scores range from 0 (worst) to 100 (best)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese
• Official Title: 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
• Brief Summary: 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: 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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention 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 (Participant, Investigator)
Masking Description:

In regards to bimagrumab and placebo-bimagrumab, the participants, Investigator and Sponsor will be blinded.

Due to semaglutide being pre-filled, packaged and labeled by manufacturer, it is not possible to blind semaglutide.

Primary Purpose: Treatment

Condition

• Obesity
• Obese
• Overweight or Obesity

Intervention

• Biological: Bimagrumab
  Human monoclonal antibody to the activin receptor type II
• Drug: Semaglutide
  Glucagon-like peptide-1 (GLP-1) receptor agonist
  Other Names:

  • Wegovy
  • Ozempic
• Other: Bimagrumab Placebo
  Placebo

Study Arms

• Placebo Comparator: Placebo to bimagrumab 30 mg/kg + no semaglutide
  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.
  Interventions:

  • Biological: Bimagrumab
  • Other: Bimagrumab Placebo
• Placebo + semaglutide 1.0 mg
  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.
  Interventions:

  • Drug: Semaglutide
  • Other: Bimagrumab Placebo
• Placebo + semaglutide 2.4 mg
  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.
  Interventions:

  • Drug: Semaglutide
  • Other: Bimagrumab Placebo
• Experimental: Bimagrumab 10 mg/kg to bimagrumab 30 mg/kg + no semaglutide
  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.
  Intervention: Biological: Bimagrumab
• Bimagrumab 10 mg/kg + semaglutide 1.0 mg
  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.
  Interventions:

  • Biological: Bimagrumab
  • Drug: Semaglutide
• Bimagrumab 10 mg/kg + semaglutide 2.4 mg
  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.
  Interventions:

  • Biological: Bimagrumab
  • Drug: Semaglutide
• Experimental: Bimagrumab 30 mg/kg + no semaglutide
  Participants will receive i.v. bimagrumab 30 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64.
  Intervention: Biological: Bimagrumab
• Bimagrumab 30 mg/kg + semaglutide 1.0 mg
  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.
  Interventions:

  • Biological: Bimagrumab
  • Drug: Semaglutide
• Bimagrumab 30 mg/kg + semaglutide 2.4 mg
  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.
  Interventions:

  • Biological: Bimagrumab
  • Drug: Semaglutide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 9, 2023): 507
• Original Estimated Enrollment (submitted: November 9, 2022): 450
• Estimated Study Completion Date: June 17, 2025
• Estimated Primary Completion Date: May 20, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand, United States
• Removed Location Countries: Brazil

Administrative Information

• NCT Number: NCT05616013
• Other Study ID Numbers: 18828; J4Z-MC-GIDA ( Other Identifier: Eli Lilly and Company ); VER201-PH2-031 ( Other Identifier: Versanis )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Versanis Bio, Inc.
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Versanis Bio, Inc.
• Collaborators: Versanis Bio, Inc.

Investigators

• Study Chair: Kenneth Attie, MD; Versanis Biotechnology

• PRS Account: Eli Lilly and Company
• Verification Date: January 2024