Objectives: Disease-modifying
therapies for
amyotrophic lateral sclerosis (ALS) are still not satisfactory. The
Rho kinase (ROCK) inhibitor
fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years,
fasudil has been approved in Japan for the treatment of vasospasm in patients with
subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose
fasudil as a disease-modifying
therapy for ALS patients. Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of
fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion
therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg
fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect
biological fluids to assess target engagement and evaluate potential
biomarkers for
disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France. Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor
fasudil in early-stage ALS-patients that started patient recruitment in 2019.