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: November 13, 2023
• Sponsor: Eli Lilly and Company
• Collaborator: Versanis Bio, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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

Condition or disease	Intervention/treatment	Phase
Obesity; Obese; Overweight or Obesity	Biological: Bimagrumab; Drug: Semaglutide; Other: Bimagrumab Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 507 participants
• 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 The extension period is then followed by a 32-week post-treatment period, during which all study treatments will be withdrawn from all arms.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
• 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
• Actual Study Start Date: November 16, 2022
• Estimated Primary Completion Date: May 31, 2024
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm	Intervention/treatment
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.	Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II; Other: Bimagrumab Placebo; 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.	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Wegovy; Ozempic; Other: Bimagrumab Placebo; 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.	Drug: Semaglutide; Glucagon-like peptide-1 (GLP-1) receptor agonist; Other Names: Wegovy; Ozempic; Other: Bimagrumab Placebo; 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.	Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
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.	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
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.	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
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.	Biological: Bimagrumab; Human monoclonal antibody to the activin receptor type II
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.	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
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.	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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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).
2. 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.
3. 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.
4. 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.
5. 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).
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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)
14. 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

15. 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
16. 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.
17. 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)
18. 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)

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Alabama

Versanis Investigational Site

Anniston, Alabama, United States, 36207

Versanis Investigational Site

Cullman, Alabama, United States, 35055

United States, Florida

Versanis Investigational Site

Hialeah, Florida, United States, 33012

Versanis Investigational Site

Jacksonville, Florida, United States, 32256

Versanis Investigational Site

Lake Worth, Florida, United States, 33461

United States, Louisiana

Versanis Investigational Site

Baton Rouge, Louisiana, United States, 70808

United States, New York

Versanis Investigational Site

New York, New York, United States, 10021

United States, North Carolina

Versanis Investigational Site

Monroe, North Carolina, United States, 28112

United States, South Carolina

Versanis Investigational Site

Columbia, South Carolina, United States, 29322

United States, Texas

Versanis Investigational Site

Sugar Land, Texas, United States, 77479

Australia

Versanis Investigational Site

Brookvale, Australia

Versanis Investigational Site

Camberwell, Australia

Versanis Investigational Site

Heidelberg Heights, Australia

Versanis Investigational Site

Morayfield, Australia

Versanis Investigational Site

Saint Leonards, Australia

Versanis Investigational Site

Sippy Downs, Australia

Versanis Investigational Site

South Brisbane, Australia

Versanis Investigational Site

Southport, Australia

Brazil

Versanis Investigational Site

Portugueses, Portuguese, Brazil

New Zealand

Versanis Investigational Site

Auckland, New Zealand

Versanis Investigational Site

Christchurch, New Zealand

Versanis Investigational Site

Hamilton, New Zealand

Versanis Investigational Site

Nelson, New Zealand

Versanis Investigational Site

Wellington, New Zealand

Sponsors and Collaborators

Eli Lilly and Company

Versanis Bio, Inc.

Investigators

• Study Chair: Kenneth Attie, MD; Versanis Biotechnology

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT05616013
• Other Study ID Numbers: 18828; VER201-PH2-031 ( Other Identifier: Eli Lilly and Company )
• First Posted: November 14, 2022
• Last Update Posted: November 13, 2023
• Last Verified: November 2023

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

Keywords provided by Eli Lilly and Company:

bimagrumab; semaglutide

Additional relevant MeSH terms:

Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Antibodies, Monoclonal; Antibodies, Blocking; Immunologic Factors; Physiological Effects of Drugs