A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS
dc.contributor.author | Shefner, Jeremy M. | |
dc.contributor.author | Andrews, Jinsy A. | |
dc.contributor.author | Genge, Angela | |
dc.contributor.author | Jackson, Carlayne | |
dc.contributor.author | Lechtzin, Noah | |
dc.contributor.author | Miller, Timothy M. | |
dc.contributor.author | Cockroft, Bettina M. | |
dc.contributor.author | Meng, Lisa | |
dc.contributor.author | Wei, Jenny | |
dc.contributor.author | Wolff, Andrew A. | |
dc.contributor.author | Malik, Fady I. | |
dc.contributor.author | Bodkin, Cynthia | |
dc.contributor.author | Brooks, Benjamin R. | |
dc.contributor.author | Caress, James | |
dc.contributor.author | Dionne, Annie | |
dc.contributor.author | Fee, Dominic | |
dc.contributor.author | Goutman, Stephen A. | |
dc.contributor.author | Goyal, Namita A. | |
dc.contributor.author | Hardiman, Orla | |
dc.contributor.author | Hayat, Ghazala | |
dc.contributor.author | Heiman-Patterson, Terry | |
dc.contributor.author | Heitzman, Daragh | |
dc.contributor.author | Henderson, Robert D. | |
dc.contributor.author | Johnston, Wendy | |
dc.contributor.author | Karam, Chafic | |
dc.contributor.author | Kiernan, Matthew C. | |
dc.contributor.author | Kolb, Stephen J. | |
dc.contributor.author | Korngut, Lawrence | |
dc.contributor.author | Ladha, Shafeeq | |
dc.contributor.author | Matte, Genevieve | |
dc.contributor.author | Mora, Jesus S. | |
dc.contributor.author | Needham, Merrilee | |
dc.contributor.author | Oskarsson, Bjorn | |
dc.contributor.author | Pattee, Gary L. | |
dc.contributor.author | Pioro, Erik P. | |
dc.contributor.author | Pulley, Michael | |
dc.contributor.author | Quan, Dianna | |
dc.contributor.author | Rezania, Kourosh | |
dc.contributor.author | Schellenberg, Kerri L. | |
dc.contributor.author | Schultz, David | |
dc.contributor.author | Shoesmith, Christen | |
dc.contributor.author | Simmons, Zachary | |
dc.contributor.author | Statland, Jeffrey | |
dc.contributor.author | Sultan, Shumaila | |
dc.contributor.author | Swenson, Andrea | |
dc.contributor.author | Van Den Berg, Leonard H. | |
dc.contributor.author | Vu, Tuan | |
dc.contributor.author | Vucic, Steve | |
dc.contributor.author | Weiss, Michael | |
dc.contributor.author | Whyte-Rayson, Ashley | |
dc.contributor.author | Wymer, James | |
dc.contributor.author | Zinman, Lorne | |
dc.contributor.author | Rudnicki, Stacy A. | |
dc.contributor.department | Neurology, School of Medicine | en_US |
dc.date.accessioned | 2022-11-14T18:17:41Z | |
dc.date.available | 2022-11-14T18:17:41Z | |
dc.date.issued | 2021-05 | |
dc.description.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). | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Shefner JM, Andrews JA, Genge A, et al. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021;22(3-4):287-299. doi:10.1080/21678421.2020.1822410 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/30538 | |
dc.language.iso | en_US | en_US |
dc.publisher | Taylor & Francis | en_US |
dc.relation.isversionof | 10.1080/21678421.2020.1822410 | en_US |
dc.relation.journal | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Amyotrophic lateral sclerosis | en_US |
dc.subject | Randomized clinical trial | en_US |
dc.subject | Reldesemtiv | en_US |
dc.title | A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS | en_US |
dc.type | Article | en_US |