Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Amyotrophic lateral sclerosis and frontotemporal degeneration, 2021-05, Vol.22 (3-4), p.287-299

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2021

Beschreibungen/Notizen

• 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)