VITALITY-ALS, a phase III trial of tirasemtiv, a selective fast skeletal muscle troponin activator, as a potential treatment for patients with amyotrophic lateral sclerosis: study design and baseline characteristics.
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.
['Andrews|Jinsy A|JA|', 'Cudkowicz|Merit E|ME|', 'Hardiman|Orla|O|', 'Meng|Lisa|L|', 'Bian|Amy|A|', 'Lee|Jacqueline|J|', 'Wolff|Andrew A|AA|', 'Malik|Fady I|FI|', 'Shefner|Jeremy M|JM|']
D000690:Amyotrophic Lateral Sclerosis D004311:Double-Blind Method D005260:Female D005500:Follow-Up Studies D006801:Humans D007093:Imidazoles D008297:Male D011719:Pyrazines D012720:Severity of Illness Index D014336:Troponin
Tirasemtiv amyotrophic lateral sclerosis slow vital capacity