Inhibition of Rho Kinase (ROCK) With Fasudil as Disease-modifying Treatment for ALS

Summary

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder and therapeutic options are limited. The rho kinase (ROCK) inhibitor Fasudil was shown to be neuroprotective, induced axonal regeneration and improved survival and behavioral outcome in models of ALS and other neurodegenerative diseases. The aim of this phase IIa, multi-center and double-blind study is to analyze the safety, tolerability and efficacy of fasudil in two different doses compared to placebo in approximately 16 trial sites in Germany, France and Switzerland. Intravenous application of fasudil will be performed in 80 patients and placebo in 40 patients two times daily for 20 treatment days. The hypothesis is that fasudil is safe and well-tolerated and its application will significantly improve the clinical outcome in patients with ALS.

Timeline

Start

2019-02-20

Primary completion

2022-11-30

Completion

2023-11-01

Publications

• Background Lingor P, Weber M, Camu W, Friede T, Hilgers R, Leha A, Neuwirth C, Gunther R, Benatar M, Kuzma-Kozakiewicz M, Bidner H, Blankenstein C, Frontini R, Ludolph A, Koch JC; ROCK-ALS Investigators. ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis. Front Neurol. 2019 Mar 27;10:293. doi: 10.3389/fneur.2019.00293. eCollection 2019.
• Wolff AW, Leha A, Koch JC, Demleitner AF, Neuwirth C, Friede T, Weber M, Lingor P. Effects of fasudil on disease spreading in ALS - A MUNIX-based post-hoc analysis of the ROCK-ALS trial. Neurotherapeutics. 2026 Jun 3;23(4):e00936. doi: 10.1016/j.neurot.2026.e00936. Online ahead of print.
• Koch JC, Leha A, Bidner H, Cordts I, Dorst J, Gunther R, Zeller D, Braun N, Metelmann M, Corcia P, De La Cruz E, Weydt P, Meyer T, Grosskreutz J, Soriani MH, Attarian S, Weishaupt JH, Weyen U, Kuttler J, Zurek G, Rogers ML, Feneberg E, Deschauer M, Neuwirth C, Wuu J, Ludolph AC, Schmidt J, Remane Y, Camu W, Friede T, Benatar M, Weber M, Lingor P; ROCK-ALS Study group. Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis (ROCK-ALS): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2024 Nov;23(11):1133-1146. doi: 10.1016/S1474-4422(24)00373-9.
• Lingor P, Koch JC, Statland JM, Hussain S, Hennecke C, Wuu J, Langbein T, Ahmed R, Gunther R, Ilse B, Kassubek J, Kollewe K, Kuttler J, Leha A, Lengenfeld T, Meyer T, Neuwirth C, Tostmann R, Benatar M. Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug;22(5-6):419-425. doi: 10.1080/21678421.2021.1879866. Epub 2021 Feb 3.

Drugs

Indications