Trial Outcomes & Findings for Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese (NCT NCT05616013)

The study was designed to be conducted in three phases: Core Treatment period (Weeks 1 to 48) followed by Open Label Extension Treatment Period (Weeks 49 to 72) and Post-Treatment Follow-Up Period (Weeks 73 to 104) Currently, only the results from the Core Treatment phase (up to Week 48) are available. Data from Open Label Extension (up to Week 72) and Post-Treatment Follow-Up (up to Week 104) are still being analyzed and will be reported at the time of final results reporting by June 2026.

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

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

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.

Waist circumference was measured in standing position with a non-stretchable measuring tape to the nearest 0.1 cm.

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.

Fat mass was obtained by DXA and was used to assess changes in body composition.

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.

Percent body fat obtained by DXA was used to assess changes in body composition.

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

DXA was used to assess changes in body composition.

Waist circumference was measured in a standing position with a non-stretchable measuring tape to the nearest 0.1 cm.

Body weight was measured in kgs to the nearest 0.1 kg.

DXA was used to assess the changes in body composition.

DXA was used to assess changes in body composition.

DXA was used to assess changes in body composition. FLI=% change in fat mass / % change in lean mass + % change in fat mass.

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.

Body fat mass was assessed through BIA.

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.

Body fat percentage was assessed through BIA.

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

Lean mass was assessed through DXA.

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

DXA was used to assess changes in body composition.

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.

DXA was used to assess changes in body composition.

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.

BIA is a widely used method for estimating body composition.

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.

BIA is a widely used method for estimating body composition.

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/m2

WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6

WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6

WHtR ratio categories: \<0.5; 0.5-0.59; ≥0.6

HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

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.

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.

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

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.

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.

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.'

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.'

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.'