A Study of the Effect of BIIB023 on Muscle Atrophy in Healthy Male Volunteers

Study Overview
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Brief Summary
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The primary objective of this study is to determine whether muscle atrophy induced by immobilization of the lower limb can be attenuated by BIIB023 in healthy male volunteers. The secondary objectives of this study in this study population are: To determine whether muscle weakness induced by immobilization of the lower limb can be attenuated by BIIB023 To assess the effect of BIIB023 on the recovery of muscle mass and strength after immobilization To assess the effect of BIIB023 on histological markers of muscle atrophy and regeneration To assess the effect of BIIB023 on muscle bioenergetics based on oxidative metabolism recovery kinetics To evaluate the safety and tolerability of BIIB023

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of Intravenous BIIB023 (Anti-TWEAK) on Lower Limb Muscle Mass and Strength During and After Knee-Joint Immobilization in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: BIIB023
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Deemed healthy as determined by the Investigator based on medical history, 12-lead electrocardiogram, vital signs, and clinical laboratory parameters at Screening, and physical examination at Baseline Body mass index (BMI) between 18.5 and 32 kg/m2, inclusive, at the time of Screening Willing to abstain from using tobacco and tobacco-containing products during the study Willing to limit the intake of alcohol to no more than 2 units per day throughout the study; exceptions are 48 hours prior to Screening, 48 hours prior to Day 1, and during the in-clinic immobilization period when no alcohol will be permitted. One unit of alcohol is defined as 12 fluid ounce (fl oz) of beer, 5 fl oz of wine, or 1.5 fl oz of liquor Willing to maintain a regular diet for the duration of the study and a recreational level of physical activity defined as participation in an exercise program or other physical activity at a level of intensity that does not exceed the level prior to study entry Practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after the last dose of study treatment. Key Exclusion Criteria: History of or positive test result at Screening for human immunodeficiency virus (HIV). History or positive test result at Screening for hepatitis C virus (HCV) antibody or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). History of tuberculosis (TB) or a positive QuantiFERON®-TB Gold test. There must be no other clinical evidence of TB on physical examination of the subject. Use of tobacco or tobacco-containing products within 3 months prior to Screening Known history of thrombophilia, hypercoagulopathy, or prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE) History of physical activity consistent with endurance training or resistance training within 6 months prior to Screening Any back, leg, knee, or shoulder complaints that may interfere with the use of crutches Prolonged travel (more than 6 hours) within 2 weeks prior to randomization. NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB023<br>Participants receive intravenous (IV) infusions of BIIB023 | Biological: BIIB023<br>* Intravenous (IV) infusions<br>* Other names: (anti-TWEAK [TNF-related Weak Inducer of Apoptosis] monoclonal antibody);|
| Placebo Comparator: Placebo<br>Participants receive intravenous (IV) infusions of placebo | Biological: Placebo<br>* Matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in the magnitude of muscle atrophy |  | between Day 14 and Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in the magnitude of muscle atrophy, measured by T1W-MRI analysis of the CSA of the triceps surae muscles of the immobilized limb |  | between Day 14 and Day 42 | 
| Percentage change in isometric knee-extension strength (torque), measured by dynamometry |  | between Day 14 and Day 42 | 
| Percentage change in isometric plantar-flexion strength (torque), measured by dynamometry |  | between Day 14 and Day 42 | 
| Percentage change in total CSA of Type I and II fibers, measured by histological analysis of muscle biopsy |  | between Day 14, Day 21, and Day 42 | 
| Change in density of satellite cells and other molecular markers of muscle regeneration, measured by histological analysis of muscle biopsy |  | between Day 14, Day 21, and Day 42 | 
| Change in the recovery of muscle oxidative metabolism, measured by near-infrared spectroscopy (NIRS) of the quadriceps femoris muscles |  | between Day 14 and Day 42 | 
| The number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 156 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle Disuse Atrophy