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000278570 1001_ $$aShefner, Jeremy M$$b0
000278570 245__ $$aReldesemtiv in Amyotrophic Lateral Sclerosis: Results From the COURAGE-ALS Randomized Clinical Trial.
000278570 260__ $$aChicago, Ill.$$bAmerican Medical Association$$c2025
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000278570 520__ $$aTreatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression.To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS.A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (COURAGE-ALS) was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted at 83 ALS centers in 16 countries from August 2021 to July 2023. The first 24-week period was placebo controlled vs reldesemtiv. All participants received reldesemtiv during the second 24-week period with a 4-week follow-up. Two interim analyses were planned, the first for futility and the second for futility and possible resizing. This was a hybrid decentralized trial with approximately half the trial visits performed remotely and the remaining visits in the clinic. Eligible participants met criteria for definite, probable, or possible ALS with lower motor neuron signs by modified El Escorial Criteria, ALS symptoms for 24 months or less, ALS Functional Rating Scale-Revised (ALSFRS-R) total score of 44 or less, and forced vital capacity of greater than or equal to 65% of predicted.Oral reldesemtiv, 300 mg, or placebo twice daily.The primary end point was change in ALSFRS-R total score from baseline to week 24.Of the 696 participants screened, 207 were screen failures. A total of 486 participants (mean [SD] age, 59.4 [10.9] years; 309 male [63.6%]) were randomized to reldesemtiv (n = 325) or placebo (n = 161); 3 randomized patients were not dosed. The second interim analysis at 24 weeks after randomization included 256 participants. The data monitoring committee recommended that the trial should end due to futility, and the sponsor agreed. The mean (SE) group difference in the ALSFRS-R score from baseline to week 24 was -1.1 (0.53; 95% CI, -2.17 to -0.08; P = .04, favoring placebo). Given excess missing data from early termination, the combined assessment assumed greater importance; it, too, failed to show a benefit from treatment with reldesemtiv (win probability was 0.44 for reldesemtiv and 0.49 for placebo, with a win ratio of 0.91; 95% CI of win ratio, 0.77-1.10; P = .11).This randomized clinical trial failed to demonstrate efficacy for reldesemtiv in slowing functional decline in ALS.ClinicalTrials.gov Identifier: NCT04944784.
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000278570 650_7 $$2NLM Chemicals$$aCK-2017357
000278570 650_7 $$2NLM Chemicals$$aOxadiazoles
000278570 650_7 $$04S0HBYW6QE$$2NLM Chemicals$$areldesemtiv
000278570 650_7 $$2NLM Chemicals$$aPyrazines
000278570 650_7 $$2NLM Chemicals$$aPyrimidines
000278570 650_7 $$2NLM Chemicals$$aImidazoles
000278570 650_7 $$2NLM Chemicals$$aPyrroles
000278570 650_7 $$2NLM Chemicals$$aPyridines
000278570 650_2 $$2MeSH$$aHumans
000278570 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: drug therapy
000278570 650_2 $$2MeSH$$aMale
000278570 650_2 $$2MeSH$$aFemale
000278570 650_2 $$2MeSH$$aMiddle Aged
000278570 650_2 $$2MeSH$$aDouble-Blind Method
000278570 650_2 $$2MeSH$$aAged
000278570 650_2 $$2MeSH$$aTreatment Outcome
000278570 650_2 $$2MeSH$$aOxadiazoles: therapeutic use
000278570 650_2 $$2MeSH$$aDisease Progression
000278570 650_2 $$2MeSH$$aPyrazines
000278570 650_2 $$2MeSH$$aPyrimidines
000278570 650_2 $$2MeSH$$aImidazoles
000278570 650_2 $$2MeSH$$aPyrroles
000278570 650_2 $$2MeSH$$aPyridines
000278570 7001_ $$aCudkowicz, Merit E$$b1
000278570 7001_ $$aGenge, Angela$$b2
000278570 7001_ $$aHardiman, Orla$$b3
000278570 7001_ $$aAl-Chalabi, Ammar$$b4
000278570 7001_ $$aAndrews, Jinsy A$$b5
000278570 7001_ $$aChio, Adriano$$b6
000278570 7001_ $$aCorcia, Philippe$$b7
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000278570 7001_ $$aMaragakis, Nicholas J$$b15
000278570 7001_ $$aMiller, Timothy M$$b16
000278570 7001_ $$aMora, Jesus S$$b17
000278570 7001_ $$aPetri, Susanne$$b18
000278570 7001_ $$aSimmons, Zachary$$b19
000278570 7001_ $$avan den Berg, Leonard H$$b20
000278570 7001_ $$aZinman, Lorne$$b21
000278570 7001_ $$aKupfer, Stuart$$b22
000278570 7001_ $$aMalik, Fady I$$b23
000278570 7001_ $$aMeng, Lisa$$b24
000278570 7001_ $$aSimkins, Tyrell J$$b25
000278570 7001_ $$aWei, Jenny$$b26
000278570 7001_ $$aWolff, Andrew A$$b27
000278570 7001_ $$aRudnicki, Stacy A$$b28
000278570 7001_ $$aGroup, COURAGE-ALS Study$$b29$$eCollaboration Author
000278570 7001_ $$aKiernan, Matthew C$$b30$$eContributor
000278570 7001_ $$aSchultz, David$$b31$$eContributor
000278570 7001_ $$aNeedham, Merrilee$$b32$$eContributor
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000278570 7001_ $$aAttarian, Shahram$$b46$$eContributor
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