Authors
Jeremy M Shefner, Merit E Cudkowicz, Orla Hardiman, Bettina M Cockroft, Jacqueline H Lee, Fady Malik, Lisa Meng, Stacy A Rudnicki, Andrew A Wolff, Jinsy A Andrews, Philip Van Damme, Lawrence Korngut, Wendy Johnston, Colleen O'Connell, Ian Grant, John Turnbull, Christen Shoesmith, Lorne Zinman, Stephan Botez, Angela Genge, Annie Dionne, Philippe Couratier, Shahram Attarian, Jean Pouget, William Camu, Claude Desnuelle, Francois Salachas, Philippe Corcia, Thomas Meyer, Susanne Petri, Albert Ludolph, Andrea Calvo, Christian Lunetta, Vincenzo Silani, Leonard van den Berg, Mamede de Carvalho, Jesus Mora Pardina, Carolyn Young, Ammar Al-Chalabi, Aleksander Radunovic, Clemens Hanemann, Shafeeq Ladha, Namita Goyal, John Ravits, Richard Lewis, Nanette Joyce, Bjorn Oskarsson, Jonathan S Katz, Yuen So, Dianna Quan, Kevin Felice, Elham Bayat, Kevin Boylan, Michael G Benatar, Vu Tuan, Jonathan Glass, Robert Sufit, Cynthia Bodkin, Andrea Swenson, Jeffrey Statland, Nicholas Maragakis, James Berry, Robert Brown, Johnny Salameh, Stephen Goutman, Daniel S Newman, Gaurav Guliani, Samuel Maiser, Alan Pestronk, Ghazala Hayat, Gary Pattee, Jeffrey Cohen, Benjamin Brooks, Richard Bedlack, James Caress, Hiroshi Mitsumoto, Dale Lange, Deborah Bradshaw, Stephen J Kolb, Chafic Karam, Julie Khoury, Kimberly Goslin, Zachary Simmons, Leo Mc Cluskey, Terry Heiman-Patterson, Peter Donofrio, Daragh Heitzman, Yadollah Harati, Carlayne Jackson, Lawrence Phillips, Michael Weiss, Christopher Nance, Shumaila Sultan, Paul Barkhaus
Publication date
2019/10/2
Journal
Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration
Volume
20
Issue
7-8
Pages
584-594
Publisher
Taylor & Francis
Description
Objective: To assess the efficacy of tirasemtiv, a fast skeletal muscle troponin activator, vs. placebo in patients with amyotrophic lateral sclerosis. Methods: VITALITY-ALS (NCT02496767) was a multinational, double-blind, randomized, placebo-controlled clinical trial. Participants tolerating 2 weeks of open-label tirasemtiv (125 mg twice daily) were randomized 3: 2: 2: 2 to placebo or one of three target tirasemtiv dose levels, using an escalating dosage protocol lasting 28 days. The primary outcome measure was changed in slow vital capacity (SVC) at 24 weeks. Secondary endpoints included a change in muscle strength and time to respiratory milestones of disease progression.
Results: Of 744 participants, 565 tolerated open-label tirasemtiv and received randomized treatment. By 24 weeks, 23 (12.2%) placebo-treated participants discontinued study treatment vs. 129 (34.2%) randomized to tirasemtiv. SVC declined by 14.4%(95% CI:-16.8,-11.9) in the placebo group and 13.4%(95% CI:-15.3,-11.6) in the tirasemtiv group (p ¼ 0.56). Secondary endpoints did not show significant differences. However, participants who tolerated tirasemtiv at their randomized dose showed a numeric trend toward a dose-related slowing of decline in SVC (p= 0.11). Dizziness, fatigue, nausea, weight loss, and insomnia occurred more frequently on tirasemtiv. Serious adverse events were similar across groups. Conclusions: Tirasemtiv did not alter the decline of SVC or significantly impact secondary outcome measures. Poor tolerability of tirasemtiv may have contributed to this result. However, participants tolerating their intended dose exhibited a trend toward treatment …
Scholar articles
JM Shefner, ME Cudkowicz, O Hardiman, BM Cockroft… - Amyotrophic Lateral Sclerosis And Frontotemporal …, 2019