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A Phase 2, Double-Blind, randomized, Dose-Ranging trial Of Reldesemtiv in patients with ALS
Journal article   Open access   Peer reviewed

A Phase 2, Double-Blind, randomized, Dose-Ranging trial Of Reldesemtiv in patients with ALS

J.M. Shefner, J.A. Andrews, A. Genge, C. Jackson, N. Lechtzin, T.M. Miller, B.M. Cockroft, L. Meng, J. Wei, A.A. Wolff, …
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Vol.22(3-4), pp.287-299
2020
DOI: https://doi.org/10.1080/21678421.2020.1822410
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Abstract

To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients (N = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance (p = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p = 0.09; muscle strength mega-score, p = 0.31). Post hoc analyses pooling all active reldesemtiv-treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898)

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Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.52 Neurodegenerative Diseases
1.52.765 ALS Mechanisms
Web Of Science research areas
Clinical Neurology
ESI research areas
Neuroscience & Behavior
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