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
- COMPLETED
- Sex
- All
- Target Recruitment
- 507
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A written informed consent must be obtained before any study-related assessments are performed.
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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.
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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 Placebo Participants received a placebo administered intravenously (IV) at baseline and at weeks 4, 16, 28, and 40 during the core treatment period. Bimagrumab 10 mg/kg Bimagrumab Participants received bimagrumab 10 milligrams/kilogram (mg/kg) administered IV at baseline and at weeks 4, 16, 28, and 40 during the core treatment period. Bimagrumab 30 mg/kg Bimagrumab Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40. Placebo + Semaglutide 1.0 mg Semaglutide Participants received a placebo administered IV at baseline and at Weeks 4, 16, 28, and 40, and 1 milligram (mg) of semaglutide administered subcutaneously (SC) weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg Placebo + Semaglutide 1.0 mg Placebo Participants received a placebo administered IV at baseline and at Weeks 4, 16, 28, and 40, and 1 milligram (mg) of semaglutide administered subcutaneously (SC) weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg Placebo + Semaglutide 2.4 mg Semaglutide Participants received a placebo administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg. Placebo + Semaglutide 2.4 mg Placebo Participants received a placebo administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg. Bimagrumab 10 mg/kg + Semaglutide 1.0 mg Bimagrumab Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg. Bimagrumab 10 mg/kg + Semaglutide 1.0 mg Semaglutide Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg. Bimagrumab 10 mg/kg + Semaglutide 2.4 mg Bimagrumab Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg. Bimagrumab 10 mg/kg + Semaglutide 2.4 mg Semaglutide Participants received bimagrumab 10 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg. Bimagrumab 30 mg/kg + Semaglutide 1.0 mg Bimagrumab Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg Bimagrumab 30 mg/kg + Semaglutide 1.0 mg Semaglutide Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28, and 40, and 1 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 48: 1.0 mg Bimagrumab 30 mg/kg + semaglutide 2.4 mg Bimagrumab Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28 and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg. Bimagrumab 30 mg/kg + semaglutide 2.4 mg Semaglutide Participants received bimagrumab 30 mg/kg administered IV at baseline and at weeks 4, 16, 28 and 40, and 2.4 mg semaglutide administered SC weekly for 48 weeks as per the below dose escalation schedule: Weeks 1 to 4: 0.25 mg Weeks 5 to 8: 0.5 mg Weeks 9 to 12: 1.0 mg Weeks 13 to 16: 1.7 mg Weeks 17 to 48: 2.4 mg.
- Primary Outcome Measures
Name Time Method Change From Baseline in Body Weight at Week 48 Baseline, Week 48 Least square (LS) Mean was determined by analysis of covariance (ANCOVA) model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm
- Secondary Outcome Measures
Name Time Method Change From Baseline in Waist Circumference at Week 48 Baseline, Week 48 Waist circumference was measured in standing position with a non-stretchable measuring tape to the nearest 0.1 centimeter (cm). LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Waist Circumference at Week 72 Baseline, Week 72 Waist circumference was measured in standing position with a non-stretchable measuring tape to the nearest 0.1 cm.
Change From Baseline in Total Body Fat Mass in Kilograms (kg) at Week 48 Baseline, Week 48 Fat mass was obtained by Dual energy X-ray absorptiometry (DXA) was used to assess changes in body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Total Body Fat Mass in kg at Week 72 Baseline, Week 72 Fat mass was obtained by DXA and was used to assess changes in body composition.
Change From Baseline in Body Fat Percentage at Week 48 Baseline, Week 48 Body fat percentage was obtained by DXA was used to assess changes in body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Body Fat Percentage at Week 72 Baseline, Week 72 Percent body fat obtained by DXA was used to assess changes in body composition.
Change From Baseline in Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Trunk Fat Mass by DXA at Week 48 Baseline, Week 48 DXA was used to assess changes in body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm
Change From Baseline in VAT, SAT and Trunk Fat Mass by DXA at Week 72 Baseline, Week 72 DXA was used to assess changes in body composition.
Percentage of Participants With Reduction in Waist Circumference ≥ 5 cm at Week 48 Week 48 Waist circumference was measured in a standing position with a non-stretchable measuring tape to the nearest 0.1 cm.
Percentage of Participants With Reduction in Body Weight ≥ 5%, ≥ 10% and ≥15% at Week 48 Week 48 Body weight was measured in kgs to the nearest 0.1 kg.
Percentage of Participants With Reduction in Fat Mass ≥ 5% ≥ 10% ≥ 15% by DXA at Week 48 Week 48 DXA was used to assess the changes in body composition.
Percentage of Participants With Reduction in Fat Mass ≥ 10% With <5% Decrease (or an Increase) in Lean Mass by DXA at Week 48 Week 48 DXA was used to assess changes in body composition.
Percentage of Participants Achieving >5 kg Weight Loss and Fat Loss Index (FLI) of >70%, >80%, and >90% by DXA at Week 48 Week 48 DXA was used to assess changes in body composition. FLI=% change in fat mass / % change in lean mass + % change in fat mass.
Change From Baseline in Body Fat Mass by Bioelectrical Impedance Analysis (BIA) at Week 48 Baseline, Week 48 Body fat was assessed through BIA. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Body Fat Mass by BIA at Week 72 Baseline, Week 72 Body fat mass was assessed through BIA.
Change From Baseline in Body Fat Percentage by BIA at Week 48 Baseline, Week 48 Body fat percentage was assessed through BIA. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Body Fat Percentage by BIA at Week 72 Baseline, Week 72 Body fat percentage was assessed through BIA.
Change From Baseline in Lean Mass by DXA at Week 48 Baseline, Week 48 Lean mass was assessed through DXA. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm
Change From Baseline in Lean Mass by DXA at Week 72 Baseline, Week 72 Lean mass was assessed through DXA.
Change From Baseline in Lean Body Mass Percentage by DXA at Week 48 Baseline, Week 48 Lean body mass percentage was assessed through DXA. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm
Change From Baseline in Lean Body Mass Percentage by DXA at Week 72 Baseline, Week 72 DXA was used to assess changes in body composition.
Change From Baseline in Appendicular Lean Mass by DXA at Week 48 Baseline, Week 48 DXA was used to assess changes in body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Appendicular Lean Mass by DXA at Week 72 Baseline, Week 72 DXA was used to assess changes in body composition.
Change From Baseline in Lean Mass (kg) by BIA at Week 48 Baseline, Week 48 BIA is a widely used method for estimating body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Lean Mass (kg) by BIA at Week 72 Baseline, Week 72 BIA is a widely used method for estimating body composition.
Change From Baseline in Percentage Lean Body Mass by BIA at Week 48 Baseline, Week 48 BIA is a widely used method for estimating body composition. LS Mean was determined by ANCOVA model using Baseline + Gender (Male, Female) + Country (Australia, New Zealand, United States of America) + Treatment (Type III sum of squares) as variables. Only participants with non-missing baseline value were included in analysis. Missing values at Week 48 were imputed 100 times based on observed data in the Placebo arm.
Change From Baseline in Percentage Lean Body Mass by BIA at Week 72 Baseline, Week 72 BIA is a widely used method for estimating body composition.
Percentage of Participants With Body Mass Index (BMI) Categories at Baseline and Week 48 Baseline, Week 48 BMI categories:
i. Healthy weight: 18.5 kilograms (kg)/meter (m)² 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 Baseline Waist-to-Height Ratio (WtHR) Category of <0.5 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48 Baseline up to 48 weeks WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6
Percentage of Participants With Baseline WtHR Category of 0.5-0.59 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48 Baseline up to 48 weeks WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6
Percentage of Participants With Baseline WtHR Category ≥0.6 Having Change From Baseline in Waist-to-Height Ratio (WHtR Ratio) Categories at Week 48 Baseline up to 48 weeks WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 48 Baseline, 48 weeks HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Change From Baseline in Quality of Life Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 24 Baseline, Week 24 The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores.
Change From Baseline in Quality of Life SF-36v2 Acute Form Total Score Week 24 Baseline, Week 24 The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into (mental component score \[MCS\] and physical componenet score \[PCS\] to obtain a total score ranging from 0 to 100, with higher scores indicating better levels of function and/or better health.
Change From Baseline in Quality of Life SF-36v2 Acute Form Physical Functioning Domain Score Week 48 Baseline, Week 48 The SF-36v2 acute form assesses HRQoL on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10 items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores
Change From Baseline in Quality of Life SF-36v2 Acute Form Total Score at Week 48 Baseline, Week 48 The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into MCS and PCS to obtain a total score ranging from 0 to 100, with higher scores indicating better levels of function and/or better health.
Change From Baseline in Quality of Life SF-36v2 Acute Form Physical Functioning Domain Score and Total Score at Week 72 Baseline, Week 72 The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Score and Total Score at Week 24 Baseline, Week 24 The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'
Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 48 Baseline, Week 48 The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'
Change From Baseline in IWQOL-Lite-CT Physical Function Score and Total Score at Week 72 Baseline, Week 72 The IWQOL-Lite-CT is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning and quality of life. This endpoint shows results for 'physical function score' and 'total score.'
Trial Locations
- Locations (26)
Middlemore Hospital
🇳🇿Auckland, 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
Clinical Neuroscience Solutions Inc
🇺🇸Jacksonville, Florida, United States
Altus Research
🇺🇸Lake Worth, Florida, United States
Pennington Biomedical Research Center
🇺🇸Baton Rouge, Louisiana, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Monroe Biomedical Research
🇺🇸Monroe, North Carolina, United States
SPICA Clinical
🇺🇸Columbia, South Carolina, United States
Scroll for more (16 remaining)Middlemore Hospital🇳🇿Auckland, New Zealand