A 24-week Off-drug Extension Study in Sarcopenic Elderly Who Completed Treatment in the 6-month Core Study

Study Overview
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Brief Summary
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This extension study was a 24-week off-drug follow-up of the core CBYM338E2202 (NCT ) study and the main objective was to determine the long-term durability of bimagrumab (BYM338) effect after a 6-month treatment period.

Detailed Description
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Two populations were defined as below: Population I: Patients enrolled prior to the protocol amendment 1, who received bimagrumab 70 mg, 210 mg or 700 mg in the core study, were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Patients receiving placebo in the core study continued receiving placebo in the extension study. Population II: Patients enrolled after protocol amendment 1, who received bimagrumab 700 mg or placebo in the core study, did not receive study medication in the extension study and were followed-up per schedule defined in this protocol amendment.

Official Title
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A 24 Week Off Drug Extension, Parallel Group, Study Assessing Durability of Effect on Skeletal Muscle Strength and Function Following a 6-month Double-blind, Placebo Controlled Study Evaluating Bimagrumab in Older Adults With Sarcopenia (InvestiGAIT Extension)

Conditions
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Sarcopenia

Intervention / Treatment
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* Drug: bimagrumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criterion: - Men and postmenopausal women aged 70 years or older that have participated in, and have completed the full study treatment period per protocol (24 weeks/EOT visit) in the preceding core study (CBYM338E2202) Exclusion criterion: - Any condition which should have led to treatment discontinuation per protocol in the core study (CBYM338E2202)

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Follow-up (arm 1)<br>Patients in Population I received 6 doses of bimagrumab 70 mg, 210 mg, 700 mg or placebo - one approximately every four weeks - over a 20-week period providing drug exposure for a total of 24 weeks. | Drug: bimagrumab<br>* bimagrumab low dose bimagrumab moderate dose bimagrumab high dose Patients enrolled prior to the protocol amendment 1 (Population I ), who received bimagrumab in the core study, entered the extension study at Week 25 and were randomly assigned to two subgroups within each of three treatment arms to either receive bimagrumab at the same dose level or placebo. Study medication was administered as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.<br>Drug: Placebo<br>* Placebo Patients enrolled prior to the protocol amendment 1 (Population I), who received placebo in core study, entered the extension study at Week 25 and received placebo as an intravenous infusion starting at Week 25 after treatment was initiated in the core study until week 45.<br>|
| No Intervention: Follow-up (arm 2)<br>Patients in Population II received either bimagrumab 700 mg or placebo in the core study and did not receive any investigational treatment in the extension study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population I: Short Physical Performance Battery (SPPB) Total Score at Week 49 | SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function). | Week 49 | 
| Population II: Short Physical Performance Battery (SPPB) Total Score at Week 49 | SPPB evaluates lower extremities in three functional components: maintenance of standing balance, usual gait speed and chair stand. Each test yields a score on a scale from 0 to 4 (total score 0-12, with the higher score reflecting a higher level of function). | Week 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population I: 6-minute Walking Distance (6MWT) at Week 49 | The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition. | Week 49 | 
| Population II: 6-minute Walking Distance (6MWT) at Week 49 | The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. A high 6MWT represent better physical condition. | Week 49 | 
| Population I: Gait Speed at Week 49 | Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed. | Week 49 | 
| Population II: Gait Speed at Week 49 | Gait Speed was assessed as part of SPPB, over a 4 meter distance of a 6 meter course. Gait speed assesses a person's usual walking speed, which is defined as the speed a person normally walks from one place to another. Poor functional performance is measured by slow or declining gait speed. | Week 49 | 
| Population I: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 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 (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. | Week 49 | 
| Population II: Appendicular Skeletal Muscle Index (ASMI) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | 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 (m2). Therefore, an increase in ASMI indicates an increase in the quantity of an individual's lean mass. | Week 49 | 
| Population I: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect | Week 49 | 
| Population II: Total Lean Body Mass (LBM) as Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 49 | LBM is defined as the Total soft tissue fat-free body mass. A high LBM represents better pharmacodynamic effect | Week 49 | 

 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, lean body mass, gait speed