Table 3.

Overview of reported key clinical trials on skeletal muscle activators.

Drug Name	Trial and Year(s)	Study Design	(n) Targeted Population	Aim	Key Findings	Ref.
Tirasemtiv (formerly known as CK-2017357)	NCT01709 149 BENEFIT-ALS 2012–2014	Multi-national, double-blind, randomised, placebo-controlled study	(596) Patients with ALS	To evaluate the safety and effectiveness of CK-2017357 when taken with or without riluzole in patients with ALS	-Primary endpoint was not met. -Mixed results were observed for the secondary endpoints.	[77,78]
	NCT02496767 VITALITY-ALS	Multi-national, double-blind, randomised, placebo-controlled, parallel-group study	(744) Patients with ALS	To confirm and extend results from a large phase IIb trial and maximize tolerability with a slower dose escalation	-Primary and secondary endpoints did not show significant differences. -Dizziness, fatigue, nausea, weight loss, and insomnia occurred more frequently on Tirasemtiv. -Tirasemtiv was poorly tolerated.	[79,80]
	NCT02936635 VIGOR-ALS 2016–2018	Open-label extension study	(280) Patients who Completed VITALITY-ALS	To assess the long-term safety and tolerability of Tirasemtiv in patients with ALS	-No available data	[81]
Reldesemtiv (CK-2127107)	NCT03065959 2017	Randomised, double-blinded study	(42) Elderly patients with muscle fatigue	To evaluate the effect of Reldesemtiv in elder patients with muscle fatigue	-Trial terminated	[69]
	NCT03160898 FORTITUDE-ALS 2018–2019	Double-blind, randomised, dose-ranging, placebo-controlled parallel group study	(458) Patients with ALS	To evaluate effect of CK-2127107 vs. placebo on respiratory function and other measures of skeletal muscle function in patients with ALS	-No statistical significance In the primary endpoint of change from baseline in SVC after 12 weeks of treatment -All Reldesemtiv groups had declined SVC and ALSFRS-R less than patients on placebo	[71]

ALS, amyotrophic lateral sclerosis; BNP, B-type natriuretic peptide; SVC, slow vital capacity; ALSFRS-R, ALS Functional Rating Scale.