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

Sponsor

Versanis Bio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05616013

Collaborator

(none)

450

Enrollment

Locations

Arms

21.5

Anticipated Duration (Months)

64.3

Patients Per Site

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

The study is designed as a factorial of 3 semaglutide doses (none, 1.0 mg and 2.4 mg) and 3 bimagrumab doses (0, 10 and 30 mg/kg).The study is designed as a factorial of 3 semaglutide doses (none, 1.0 mg and 2.4 mg) and 3 bimagrumab doses (0, 10 and 30 mg/kg).

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 :

Nov 16, 2022

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Bimagrumab placebo Participants will receive i.v. bimagrumab placebo at baseline, and at Weeks 4, 16, 28 and 40	Other: Bimagrumab Placebo Placebo
Other: Bimagrumab placebo + 1.0 mg semaglutide Participants will receive i.v. bimagrumab placebo at baseline, and at Weeks 4, 16, 28 and 40, and 1.0 mg s.c. semaglutide weekly per the dose escalation schedule	Drug: Semaglutide Glucagon-like peptide-1 (GLP-1) receptor agonist Other Names: Wegovy Ozempic Other: Bimagrumab Placebo Placebo
Other: Bimagrumab placebo + 2.4 mg semaglutide Participants will receive i.v. bimagrumab placebo at baseline, and at Weeks 4, 16, 28 and 40, and 2.4 mg s.c. semaglutide 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: 10 mg/kg bimagrumab Participants will receive 10 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16, 28 and 40	Biological: Bimagrumab Human monoclonal antibody to the activin receptor type II
Other: 10 mg/kg bimagrumab + 1.0 mg semaglutide Participants will receive 10 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16, 28 and 40, and 1.0 mg s.c. semaglutide 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
Other: 10 mg/kg bimagrumab + 2.4 mg semaglutide Participants will receive 10 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16. 28 and 40, and 2.4 mg s.c. semaglutide 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: 30 mg/kg bimagrumab Participants will receive 30 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16, 28 and 40	Biological: Bimagrumab Human monoclonal antibody to the activin receptor type II
Other: 30 mg/kg bimagrumab + 1.0 mg semaglutide Participants will receive 30 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16. 28, and 40, and 1.0 mg s.c. semaglutide 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
Other: 30 mg/kg bimagrumab + 2.4 mg semaglutide Participants will receive 30 mg/kg i.v. bimagrumab at baseline, and at Weeks 4, 16, 28 and 40, and 2.4 mg s.c. semaglutide 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

Change from baseline in body weight at 48 weeks [At baseline and 48 weeks]
Percent change in total body weight will be measured from baseline to 48 weeks

Secondary Outcome Measures

Absolute change from baseline in WC (cm) at 48 weeks [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).
Absolute change from baseline at 48 weeks in body fat mass in kilograms (kg) [At baseline and 48 weeks]
Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
Percent change from baseline at 48 weeks in body fat mass in kilograms (kg) [At baseline and 48 weeks]
Body weight will be measured in kilograms (kg) to the nearest 0.1 kg and reported as a percentage.
Absolute change from baseline at 48 weeks in visceral adipose tissue (VAT) or trunk fat mass by dual-energy x-ray absorptiometry (DXA) [At baseline and 48 weeks]
Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
Percent change from baseline at 48 weeks in visceral adipose tissue (VAT) or trunk fat mass by dual-energy x-ray absorptiometry (DXA) [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 [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 ≥ 10% [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% [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 48 weeks with change in Fat mass ≥ 10% with <5% decrease (or increase) in lean mass [At baseline and 48 weeks]
Dual energy X-ray absorptiometry (DXA) will be used to assess body composition.
Percentage of weight loss due to fat mass or lean mass at 48 weeks by dual-energy x-ray absorptiometry (DXA) [At baseline and 48 weeks]
Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
Absolute change from baseline at 48 weeks in fat mass (kg) by bioelectrical impedance analysis (BIA) [At baseline and 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 at 48 weeks in fat mass (kg) by bioelectrical impedance analysis (BIA) [At baseline and 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.
Absolute change from baseline at 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA) [At baseline 48 weeks]
Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition and will be used to assess lean mass (kg)
Absolute change from baseline at 48 weeks in lean mass (kg) by dual-energy x-ray absorptiometry (DXA) [At baseline 48 weeks]
Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
Percent change from baseline 48 weeks in lean mass (percent lean mass) by bioelectrical impedance analysis (BIA) [At baseline 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.
Percent change from baseline 48 weeks in lean mass (percent lean mass) by dual energy X-ray absorptiometry (DXA) [At baseline and 48 weeks]
Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
Safety and tolerability measurements throughout 48 weeks by TEAEs [Baseline and 48 weeks]
Incidence and severity of treatment emergent adverse events (TEAEs)
Proportion of patients with change from baseline in BMI categories at 48 weeks [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 34.9 kg/m2 v. Obesity class III: ≥ 40 kg/m2
Proportion of patients with change from baseline in WHtR ratio categories at 48 weeks [At baseline and 48 weeks]
WHtR ratio categories: <0.5; 0.5-0.59; ≥0.6
To assess treatment effects on glucose metabolism in HbA1c [At baseline and 48 weeks]
Change from baseline in HbA1c (mmol/mol) at 48 weeks.
To assess treatment effects on self-reported health status quality of life [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)
To assess treatment effects on self-reported weight-related quality of life [At baseline 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, as well as the physical functioning score. Scores range from 0 (worst) to 100 (best)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 subject's safety or compliance with the protocol

Contacts and Locations

Locations

	Site	City	Country
1	Versanis Site 1	Auckland	New Zealand
2	Versanis Site 2	Auckland	New Zealand
3	Versanis Site 6	Auckland	New Zealand
4	Versanis Site 7	Christchurch	New Zealand
5	Versanis Site 3	Hamilton	New Zealand
6	Versanis Site 5	Nelson	New Zealand
7	Versanis Site 4	Wellington	New Zealand