Dose Range Finding Study of Bimagrumab in Sarcopenia

Study Overview
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Brief Summary
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The purpose of this study was to determine the efficacy of repeat dosing with multiple dose levels of bimagrumab on patient physical function, skeletal muscle mass and strength in older adults with sarcopenia. In addition, this study generated data on the safety, tolerability, and pharmacokinetics of bimagrumab in older adults with sarcopenia.

Official Title
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A 28 Week, Randomized, Double-blind, Placebo-controlled, Two-part, Multi-center, Parallel Group Dose Range Finding Study to Assess the Effect of Monthly Doses of Bimagrumab 70, 210, and 700 mg on Skeletal Muscle Strength and Function in Older Adults With Sarcopenia (InvestiGAIT)

Conditions
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Sarcopenia

Intervention / Treatment
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* Drug: bimagrumab
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Low muscle mass as confirmed by DXA; Low gait speed <0.8 m/s SPPB score less than or equal to 9; Weigh at least 35 kg; Adequate dietary intake; Exclusion Criteria: A lower limb fracture in the past 6 months or any impairment or disease severely affecting gait (e.g. stroke with hemiparesis, myasthenia gravis, Parkinson's disease, peripheral polyneuropathy, intermittent claudication in advanced peripheral vascular disease, spinal stenosis, or severe osteoarthritis of the knee or hip with ineffective pain management); Requires regular assistance from another person for general activities of daily living (e.g. bathing, dressing, toileting). Intraocular surgery and laser procedures for refractive correction within 6 months prior to screening; Any underlying muscle disease including active myopathy or muscular dytrophy; Confirmed diagnosis of heart failure classified as New York Heart Association Class III or IV (e.g. dilated cardiomyopathy); Type I diabetes or uncontrolled Type 2 diabetes; Chronic kidney disease [estimated glomerular filtration rate (GFR) < 30 mL/min]; History of confirmed chronic obstructive pulmonary disease with a severity grade > 2 on the Medical Research Council Dyspnea Scale; Confirmed rheumatoid arthritis or other systemic autoimmune disease requiring immunosuppressive therapy or corticosteroids >10 mg/d prednisone equivalent; Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis); Myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (e.g. angioplasty or stent placement), or deep vein thrombosis/pulmonary embolism within 12 weeks of screening; Active cancer (i.e., under current treatment), or cancer requiring treatment in the last 5 years excluding non-melanoma skin cancers or cancers with excellent prognosis (e.g., early stage prostate or breast cancer, carcinoma in situ of the uterine cervix); Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc).

Ages Eligible for Study
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Minimum Age: 70 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BYM338 70 mg<br>BYM338 70 mg intravenous infusion | Drug: bimagrumab<br>* Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.<br>* Other names: BYM338;|
| Experimental: BYM338 210 mg<br>BYM338 210 mg intravenous infusion | Drug: bimagrumab<br>* Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.<br>* Other names: BYM338;|
| Experimental: BYM338 700 mg<br>BYM338 700 mg intravenous infusion | Drug: bimagrumab<br>* Bimagrumab will be administered as an intravenous infusion starting on Day 1 until week 21.<br>* Other names: BYM338;|
| Placebo Comparator: Placebo<br>Placebo intravenous infusion | Other: placebo<br>* Placebo will be administered as an intravenous infusion starting on Day 1 until week 21.<br>* Other names: 5% dextrose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Short Physical Performance Battery (SPPB) Score to Week 25 | Change from Baseline in total Short Physical Performance Battery (SPPB) Score to week 25; SPPB is a series of six activities involving three domains of physical function - balance, usual walking speed and rising from a chair , is commonly used globally to assess and quantify (score 0-12) lower extremity function and has been shown to predict future adverse health events. A decline of one or more points in the SPPB total score is predictive of a decrease in lower extremity function and future adverse clinical outcomes in older adults, including falls, hospitalizations, institutionalization, incident disability and death | Baseline, week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 25 in the 6 Minute Walk Test (6MWT) Distance | Change from Baseline at Week 25 in the 6 minute walk test (6MWT) distance to measure improvement in physical function | Baseline, week 25 | 
| Change From Baseline to Week 25 in Usual Gait Speed (GS) Over 4 Meters | Change from Baseline to Week 25 in usual Gait speed (GS) over 4 meters Gait speed in this study was assessed as part of the SPPB, over a 4 meter distance of a 6 meter course. This test assessed a person's usual walking speed, which was defined as the speed a person normally walks from one place to another without urgency (e.g., walking down a hallway). | baseline, week 25 | 
| Percentage Change From Baseline to Week 25 on Appendicular Skeletal Muscle Index (ASMI) Measured by Dual Energy X-ray Absorptiometry (DXA) | Change from Baseline to Week 25 on appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) Appendicular skeletal muscle index (ASMI) is a core requirement for determining the presence of sarcopenia and is calculated as the sum of the appendicular lean mass (kg) of the two upper and two lower limbs quantified by DXA, divided by height (m^2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. | baseline, week 25 | 
| Percentage Change From Baseline to Week 25 on Total Lean Body Mass Measured by Dual Energy X-ray Absorptiometry (DXA) | Change from Baseline to Week 25 on Total lean body mass and appendicular skeletal muscle index (ASMI) measured by Dual Energy X-ray Absorptiometry (DXA) total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(LBM at Visit - LBM at Baseline) / LBM at Baseline] * 100. | baseline, week 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, muscle wasting, elderly, strength, physical function, muscle, gait speed