Jinsy A Andrews1, Merit E Cudkowicz2, Orla Hardiman3, Lisa Meng4, Amy Bian4, Jacqueline Lee4, Andrew A Wolff4, Fady I Malik4, Jeremy M Shefner5. 1. a Eleanor and Lou Gehrig ALS Center, Columbia University , New York , NY , USA. 2. b Department of Neurology , Massachussetts General Hospital , Boston , MA , USA. 3. c Biomedical Sciences Institute of Neurosciences, The University of Dublin , Dublin , Ireland. 4. d Cytokinetics, Inc , South San Francisco , CA , USA , and. 5. e Department of Neurology , Barrow Neurological Institute , Phoenix , AZ , USA.
Abstract
OBJECTIVE: To assess the efficacy of tirasemtiv, a fast skeletal muscle troponin activator, vs. placebo on respiratory function and other functional measures in patients with amyotrophic lateral sclerosis (ALS). This study was designed to confirm and extend results from a large phase IIb trial and maximize tolerability with a slower dose escalation. METHODS: VITALITY-ALS (NCT02496767) was a multinational, double-blind, randomized, placebo-controlled, parallel-group study in ALS patients. Participants who tolerated two weeks of open-label tirasemtiv (125 mg twice a day) were randomized 3:2:2:2 to placebo or one of three target total daily dose levels of tirasemtiv (250, 375, or 500 mg). Participants randomized to tirasemtiv escalated their dose every two weeks to their target dose level or maximum tolerated dose. The primary outcome measure was change in slow vital capacity from baseline to 24 weeks. Secondary endpoints assessed the effect of tirasemtiv on muscle strength and certain respiratory milestones of disease progression. A four-week randomized withdrawal phase followed 48 weeks of treatment to evaluate the possibility of sustained benefit or rebound decline. RESULTS: Data collection will be complete in the fourth quarter of 2017. CONCLUSIONS: VITALITY-ALS was a phase III trial designed to evaluate the efficacy, safety, and tolerability of tirasemtiv in ALS.
RCT Entities:
OBJECTIVE: To assess the efficacy of tirasemtiv, a fast skeletal muscle troponin activator, vs. placebo on respiratory function and other functional measures in patients with amyotrophic lateral sclerosis (ALS). This study was designed to confirm and extend results from a large phase IIb trial and maximize tolerability with a slower dose escalation. METHODS: VITALITY-ALS (NCT02496767) was a multinational, double-blind, randomized, placebo-controlled, parallel-group study in ALS patients. Participants who tolerated two weeks of open-label tirasemtiv (125 mg twice a day) were randomized 3:2:2:2 to placebo or one of three target total daily dose levels of tirasemtiv (250, 375, or 500 mg). Participants randomized to tirasemtiv escalated their dose every two weeks to their target dose level or maximum tolerated dose. The primary outcome measure was change in slow vital capacity from baseline to 24 weeks. Secondary endpoints assessed the effect of tirasemtiv on muscle strength and certain respiratory milestones of disease progression. A four-week randomized withdrawal phase followed 48 weeks of treatment to evaluate the possibility of sustained benefit or rebound decline. RESULTS: Data collection will be complete in the fourth quarter of 2017. CONCLUSIONS: VITALITY-ALS was a phase III trial designed to evaluate the efficacy, safety, and tolerability of tirasemtiv in ALS.
Authors: Zoltán Papp; Piergiuseppe Agostoni; Julian Alvarez; Dominique Bettex; Stefan Bouchez; Dulce Brito; Vladimir Černý; Josep Comin-Colet; Marisa G Crespo-Leiro; Juan F Delgado; István Édes; Alexander A Eremenko; Dimitrios Farmakis; Francesco Fedele; Cândida Fonseca; Sonja Fruhwald; Massimo Girardis; Fabio Guarracino; Veli-Pekka Harjola; Matthias Heringlake; Antoine Herpain; Leo M A Heunks; Tryggve Husebye; Višnja Ivancan; Kristjan Karason; Sundeep Kaul; Matti Kivikko; Janek Kubica; Josep Masip; Simon Matskeplishvili; Alexandre Mebazaa; Markku S Nieminen; Fabrizio Oliva; Julius G Papp; John Parissis; Alexander Parkhomenko; Pentti Põder; Gerhard Pölzl; Alexander Reinecke; Sven-Erik Ricksten; Hynek Riha; Alain Rudiger; Toni Sarapohja; Robert H G Schwinger; Wolfgang Toller; Luigi Tritapepe; Carsten Tschöpe; Gerhard Wikström; Dirk von Lewinski; Bojan Vrtovec; Piero Pollesello Journal: J Cardiovasc Pharmacol Date: 2020-07 Impact factor: 3.105
Authors: Zoltán Papp; Piergiuseppe Agostoni; Julian Alvarez; Dominique Bettex; Stefan Bouchez; Dulce Brito; Vladimir Černý; Josep Comin-Colet; Marisa G Crespo-Leiro; Juan F Delgado; Istvan Édes; Alexander A Eremenko; Dimitrios Farmakis; Francesco Fedele; Cândida Fonseca; Sonja Fruhwald; Massimo Girardis; Fabio Guarracino; Veli-Pekka Harjola; Matthias Heringlake; Antoine Herpain; Leo Ma Heunks; Tryggve Husebye; Višnja Ivancan; Kristjan Karason; Sundeep Kaul; Matti Kivikko; Janek Kubica; Josep Masip; Simon Matskeplishvili; Alexandre Mebazaa; Markku S Nieminen; Fabrizio Oliva; Julius-Gyula Papp; John Parissis; Alexander Parkhomenko; Pentti Põder; Gerhard Pölzl; Alexander Reinecke; Sven-Erik Ricksten; Hynek Riha; Alain Rudiger; Toni Sarapohja; Robert Hg Schwinger; Wolfgang Toller; Luigi Tritapepe; Carsten Tschöpe; Gerhard Wikström; Dirk von Lewinski; Bojan Vrtovec; Piero Pollesello Journal: Card Fail Rev Date: 2020-07-08
Authors: Namita A Goyal; James D Berry; Anthony Windebank; Nathan P Staff; Nicholas J Maragakis; Leonard H van den Berg; Angela Genge; Robert Miller; Robert H Baloh; Ralph Kern; Yael Gothelf; Chaim Lebovits; Merit Cudkowicz Journal: Muscle Nerve Date: 2020-01-22 Impact factor: 3.217