Study of Efficacy and Safety of Bimagrumab in Patients After Hip Fracture Surgery

Study Overview
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Brief Summary
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The purpose of this study was to assess if bimagrumab is safe and effective in patients with muscle wasting (atrophy) after hip fracture surgery.

Official Title
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A 24-week Double-blind Treatment and 24-week Follow-up, Randomized, Multicenter, Placebo-controlled, Phase IIa/IIb Study to Evaluate Safety and Efficacy of i.v. Bimagrumab on Total Lean Body Mass and Physical Performance in Patients After Surgical Treatment of Hip Fracture

Conditions
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Muscle Wasting (Atrophy) After Hip Fracture Surgery

Intervention / Treatment
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* Drug: bimagrumab
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have X-ray confirmed successful hip fracture repair; Must have completed surgical wound healing; Ability to walk a specified distance with or without a walking aid; Must weigh at least 35 kg. Exclusion Criteria: Must not have history of any other lower limb fractures in the past 6 months; Must not have certain cardiovascular conditions; Must not have a chronic active infection (e.g. HIV, hepatitis B or C, etc); Must not have used high-dose corticosteroid medications for at least 3 months in the past year;

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, interventional, multicenter, placebo-controlled, phase IIa/IIb trial in patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bimagrumab 700 mg<br>Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria were treated with the bimagrumab high dose administered via intravenous infusion starting Day 1 until Week 20 | Drug: bimagrumab<br>* Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.<br>* Other names: BYM338;|
| Experimental: bimagrumab 210 mg<br>Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria were treated with the bimagrumab medium dose administered via intravenous infusion starting Day 1 until Week 20 | Drug: bimagrumab<br>* Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.<br>* Other names: BYM338;|
| Placebo Comparator: placebo<br>Approximately 70 patients who met all inclusion criteria and none of the exclusion criteria received matching placbo administered via intravenous infusion starting Day 1 until Week 20 | Other: placebo<br>* Matching placebo was administered as intravenous infusion starting on Day 1 until week 20.<br>|
| Experimental: Bimagrumab 70 mg<br>Approximately 35 patients who met all inclusion criteria and none of the exclusion criteria were treated with bimagrumad low dose administered via intravenous infusion starting Day 1 until Week 20 | Drug: bimagrumab<br>* Bimagrumab was administered as intravenous infusion starting on Day 1 until week 20.<br>* Other names: BYM338;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Lean Body Mass Measured by DXA (Dual-energy X-ray Absorptiometry) at Weeks 12 and 24 | Mixed Model for Repeated Measures (MMRM) of change from baseline in total LBM (kg) by treatment and visit To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least three doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg has been added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed | baseline, weeks 12 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Gait Speed at Week 24 (Meters/Sec) | Mixed Model for Repeated Measures (MMRM) of change from baseline in derived gait speed (m/sec) by treatment and visit To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg was added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed | Baseline, Week 24 | 
| Change From Baseline in Short Physical Performance Battery at Weeks 24 | MMRM change from baseline in total score by treatment & visit to Week 24 in physical performance measured by Short Physical Performance Battery (SPPB) that evaluates lower extremity function. Score range is 0 (worst performance) to 12 (best) to assess dose-response relationship of bimagrumab & facilitate adequate dose selection for future phase III studies, without need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from non- or minimally effective dose to a dose where maximal efficacy was expected. Original study was initiated with only 2 doses, therefore, lower 70mg arm was added to this study, changing randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, 210mg, or 700mg. Since 70mg dose was expected to show suboptimal efficacy, fewer patients were randomized to this group & it was used only for dose response modelling & not hypothesis testing. Consequently, no efficacy evaluation for 70mg were performed | Week 24 | 
| Incidence of Falls up to Week 48 | Group falls rate The frequency of having at least one fall up to Week 48 was summarized by treatment groups Incidence of falls was calculated for each arm up to Week 48. The ratio of these fall rates versus Placebo were calculated and presented as the Falls Rate Ratio. As mentioned in comment 5.1 above, the Falls Rate Ratio for Placebo does not apply because it would entail comparing the group to itself | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bimagrumab, BYM338, hip fracture, elderly, controlled clinical trial, randomized, muscle wasting, atrophy