Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese
- Conditions
- ObesityOverweight or ObesityObese
- Interventions
- Registration Number
- NCT05616013
- Lead Sponsor
- Eli Lilly and Company
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 507
-
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)
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Stable body weight (± 5 kg) within 90 days of screening, and body weight <150 kg
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Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
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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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Placebo to bimagrumab 30 mg/kg + no semaglutide Bimagrumab 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. Placebo + semaglutide 2.4 mg Bimagrumab Placebo 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. Placebo + semaglutide 1.0 mg Bimagrumab Placebo 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. Bimagrumab 10 mg/kg to bimagrumab 30 mg/kg + no semaglutide Bimagrumab 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. Bimagrumab 10 mg/kg + semaglutide 1.0 mg Bimagrumab 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. Placebo to bimagrumab 30 mg/kg + no semaglutide Bimagrumab Placebo 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. Bimagrumab 30 mg/kg + no semaglutide Bimagrumab Participants will receive i.v. bimagrumab 30 mg/kg at baseline and at Weeks 4, 16, 28, 40, 52 and 64. Bimagrumab 30 mg/kg + semaglutide 2.4 mg Bimagrumab 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. Bimagrumab 10 mg/kg + semaglutide 2.4 mg Bimagrumab 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. Bimagrumab 30 mg/kg + semaglutide 1.0 mg Bimagrumab 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. Placebo + semaglutide 1.0 mg Semaglutide 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. Placebo + semaglutide 2.4 mg Semaglutide 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. Bimagrumab 10 mg/kg + semaglutide 1.0 mg Semaglutide 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. Bimagrumab 10 mg/kg + semaglutide 2.4 mg Semaglutide 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. Bimagrumab 30 mg/kg + semaglutide 1.0 mg Semaglutide 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. Bimagrumab 30 mg/kg + semaglutide 2.4 mg Semaglutide 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.
- Primary Outcome Measures
Name Time Method Change from Baseline in Body Weight at 48 Weeks Baseline, Week 48 Change in total body weight will be measured from baseline to 48 weeks
- Secondary Outcome Measures
Name Time Method Change from Baseline in Waist Circumference (cm) at 48 and 72 Weeks Baseline, Week 48 and Baseline, Week 72 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 and 72 Weeks in Total Body Fat Mass in Kilograms (kg) Baseline, Week 48 and Baseline, Week 72 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 and 72 Weeks in Percent Body Fat Baseline, Week 48 and Baseline, Week 72 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 and 72 Weeks in Visceral Adipose Tissue (VAT), subcutaneous adipose tissue (SAT) and trunk fat mass by dual-energy x-ray absorptiometry (DXA) Baseline, Week 48 and Baseline, Week 72 Dual energy X-ray absorptiometry (DXA) will be used to assess changes in body composition.
Percentage of Participants at 48 Weeks with Reduction 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).
Percentage of Participants at 48 Weeks with Reduction in Body Weight ≥ 5%, ≥ 10% and ≥15% At baseline and 48 weeks Body weight will be measured in kilograms (kg) to the nearest 0.1 kg.
Percentage of Participants at 48 Weeks with Reduction in Fat Mass ≥ 5% ≥ 10% ≥ 15% by Dual Energy X-ray Absorptiometry (DXA) At baseline and 48 weeks Dual energy X-ray absorptiometry (DXA) will be used to assess the changes in body composition.
Percentage of Participants at 48 Weeks with Reduction in Fat Mass ≥ 10% with <5% Decrease (or an Increase) in 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.
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.
Change from Baseline at 48 and 72 Weeks in Fat Mass (kg and %) by Bioelectrical Impedance Analysis (BIA) Baseline, Week 48 and Baseline, Week 72 Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition.
Change from Baseline at 48 and 72 Weeks in Lean Mass (kg and %) and Appendicular Lean Mass by Dual Energy X-ray Absorptiometry (DXA) Baseline, Week 48 and Baseline, Week 72 Dual-energy x-ray absorptiometry (DXA) will be used to assess changes in body composition.
Change from Baseline at 48 and 72 Weeks in Lean Mass (kg and %) by Bioelectrical Impedance Analysis (BIA) Baseline, Week 48 and Baseline, Week 72 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] Baseline and 48 weeks Incidence and severity of treatment emergent adverse events (TEAEs)
Percentage of Participants with Change from Baseline in Body Mass Index (BMI) categories at 48 Weeks Baseline up to 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/m2Percentage of Participants with Change from Baseline in Waist-to-Height Ratio (WHtR ratio) Categories at 48 Weeks Baseline up to 48 weeks WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6
Change from Baseline in HbA1c (mmol/mol) at 48 Weeks Baseline, 48 weeks To assess treatment effects on glucose metabolism and HbA1c.
Change from Baseline at 24, 48 and 72 Weeks in Quality of Life Short Form 36 (SF-36) Survey Baseline, Week 24; Baseline, Week 48, and Baseline, Week 72 Change from baseline at 24, 48, and 72 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 24, 48, and 72 Weeks in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite) Baseline, Week 24; Baseline, Week 48, and Baseline, Week 72 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)
Trial Locations
- Locations (26)
Middlemore Hospital
🇳🇿Auckland, New Zealand
Emeritus Research
🇦🇺Camberwell, Australia
Lakeland Clinical Trials Waikato
🇳🇿Hamilton, New Zealand
Southern Clinical Trials Tasman
🇳🇿Nelson, New Zealand
Austin Health
🇦🇺Heidelberg Heights, Victoria, Australia
Southern Clinical Trials Ltd
🇳🇿Beckenham, Christchurch, Canterbury, New Zealand
P3 Research
🇳🇿Newtown, Wellington, New Zealand
New Zealand Clinical Research Auckland
🇳🇿Auckland, New Zealand
Optimal Clinical Trials
🇳🇿Auckland, New Zealand
New Zealand Clinical Research Christchurch
🇳🇿Christchurch, New Zealand
Pinnacle Research Group, LLC
🇺🇸Anniston, Alabama, United States
Cullman Clinical Trials
🇺🇸Cullman, Alabama, United States
Indago Research & Health Center, Inc
🇺🇸Hialeah, Florida, United States
Altus Research
🇺🇸Lake Worth, Florida, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
SPICA Clinical
🇺🇸Columbia, South Carolina, United States
Clinical Neuroscience Solutions Inc
🇺🇸Jacksonville, Florida, United States
Pennington Biomedical Research Center
🇺🇸Baton Rouge, Louisiana, United States
Monroe Biomedical Research
🇺🇸Monroe, North Carolina, United States
Mt. Olympus Medical Research
🇺🇸Sugar Land, Texas, United States
Northern Beaches Clinical Research
🇦🇺Brookvale, New South Wales, Australia
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
University of The Sunshine Coast Morayfield
🇦🇺Morayfield, Queensland, Australia
University of the Sunshine Coast Clinical Trial Centre
🇦🇺Sippy Downs, Queensland, Australia
University of The Sunshine Coast South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia