A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS

Jeremy M. Shefner, Jinsy A. Andrews, Angela Genge, Carlayne Jackson, Noah Lechtzin, Timothy M. Miller, Bettina M. Cockroft, Lisa Meng, Jenny Wei, Andrew A. Wolff, Fady I. Malik, Cynthia Bodkin, Benjamin R. Brooks, James Caress, Annie Dionne, Dominic Fee, Stephen A. Goutman, Namita A. Goyal, Orla Hardiman, Ghazala HayatTerry Heiman-Patterson, Daragh Heitzman, Robert D. Henderson, Wendy Johnston, Chafic Karam, Matthew C. Kiernan, Stephen J. Kolb, Lawrence Korngut, Shafeeq Ladha, Genevieve Matte, Jesus S. Mora, Merrilee Needham, Bjorn Oskarsson, Gary L. Pattee, Erik P. Pioro, Michael Pulley, Dianna Quan, Kourosh Rezania, Kerri L. Schellenberg, David Schultz, Christen Shoesmith, Zachary Simmons, Jeffrey Statland, Shumaila Sultan, Andrea Swenson, Leonard H.Van Den Berg, Tuan Vu, Steve Vucic, Michael Weiss, Ashley Whyte-Rayson, James Wymer, Lorne Zinman, Stacy A. Rudnicki

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Objective: 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).

Original languageEnglish (US)
Pages (from-to)287-299
Number of pages13
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number3-4
StatePublished - 2021

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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