The purpose of this study is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS.
COURAGE-ALS is a Phase 3, double-blind, randomized, placebo-controlled trial of reldesemtiv in patients aged 18 to 80 with ALS. The screening and qualification period for the trial will be no more than 21 days in duration. Approximately 555 eligible ALS patients will be randomized (2:1) to receive the following dose of reldesemtiv or placebo (stratified by riluzole use/non-use and edaravone use/non-use) for the first 24 weeks (double-blind, placebo-controlled period): * 300 mg reldesemtiv twice a day for a 600 mg total daily dose (TDD) * Placebo twice daily At the end of the 24-week double-blind, placebo-controlled period, patients will transition to the active drug period, where all patients will receive the following dose of reldesemtiv for the next 24 weeks: * 300 mg reldesemtiv twice a day for a 600 mg TDD for patients who were not down titrated during the 24 weeks of blinded dosing * 150 mg reldesemtiv twice a day for a 300 mg TDD for patients who were down titrated during the 24 weeks of blinded dosing
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
489
Reldesemtiv Oral Tablet
Placebo Oral Tablet
Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)
Change from baseline to Week 24 in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score using MMRM without multiple imputation; rating scale 0 to 48; higher scores indicate better functional status
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)
Composite Assessment of Function and Survival (CAFS) compares ranked outcomes based on change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score (0-48; higher scores indicate better function), time in months to dependence on assisted ventilation (DOAV) and time in months to death. Deceased participants are ranked by time-to-death; earliest deaths ranked the lowest. DOAV survivors are ranked more favorably than those who have died but lower than those alive and not DOAV. Non-DOAV survivors are ranked based on change in ALSFRS-R (largest decline in ALSFRS-R ranked lower than less decline or improvement in ALSFRS-R). Unitless ranked scores range from 1-482 (Full Analysis Set) with larger rank scores associated with a better outcome. Ranks were analyzed using stratified Wilcoxon test comparing the ranked scores between reldesemtiv and placebo, adjusting for baseline riluzole and edaravone use. The win probability and the ratio (reldesemtiv vs placebo) are presented.
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Ventilatory Function
Change from baseline in percent predicted forced vital capacity (FVC) using an in-clinic spirometer; a negative number for change from baseline indicates respiratory function decline relative to baseline
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Quality of Life
Change from baseline in ALSAQ-40 total score. ALSAQ-40 = Amyotrophic Lateral Sclerosis Assessment Questionnaire; summary scores range from 0 (best health status) to 100 (worst health status); ALSAQ-40 total score is calculated as the sum of the summary scores from the 5 domains; lower score corresponds to better health-related quality of life.
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St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
Phoenix, Arizona, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
University of California Irvine - ALS & Neuromuscular Center
Orange, California, United States
California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
San Francisco, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado, United States
GW Medical Faculty Associates
Washington D.C., District of Columbia, United States
University of Florida Jacksonville
Jacksonville, Florida, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
Tampa, Florida, United States
...and 74 more locations
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Handgrip Strength
Change from baseline in maximum handgrip strength (average of both hands) measured bilaterally by an electronic hand dynamometer
Time frame: Baseline to Week 24