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

Frontiers in Neurology

Helen Bidner¹  Christiane Blankenstein¹  Roberto Frontini²  Albert Ludolph³  The ROCK-ALS Investigators⁴  Daniel Zeller⁴  Teresa Lengenfeldt⁴  Jens Schmidt⁴  Jeffrey Statland⁴  Matthias Boentert⁴  Isabell Cordts⁴  Julian Grosskreutz⁴  Nathalie Braun⁴  Thorsten Grehl⁴  Marie-Hélène Soriani⁴  Philippe Corcia⁴  Eirini Zielke⁴  Thomas Meyer⁴  Susanne Petri⁴  Shahram Attarian⁴  Marcus Deschauer⁴  Josua Kuttler⁴  Joachim Schuster⁴  Fabian Maass⁴  Andreas Hermann⁴  Yvonne Remane⁴  Jochen Weishaupt⁴  Mathias Bähr⁴  Reinhard Hilgers⁵  Tim Friede⁵  Andreas Leha⁵  Magdalena Kuzma-Kozakiewicz⁶  Paul Lingor⁹  Jan C. Koch⁹  Michael Benatar^1,10  René Günther^1,11  Christoph Neuwirth^1,12  Markus Weber^1,12  William Camu^1,13 

[1] 0Münchner Studienzentrum, Technical University of Munich, Munich, Germany;1Pharmacy at the University of Leipzig Medical Center, Leipzig, Germany;2Department of Neurology, University of Ulm, Ulm, Germany;;Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany;Department of Neurology, Medical University of Warsaw, Warsaw, Poland;Department of Neurology, Technical University of Dresden, Dresden, Germany;Department of Neurology, Technical University of Munich, Munich, Germany;Department of Neurology, University Medical Center Göttingen, Göttingen, Germany;Department of Neurology, University of Miami, Miami, FL, United States;German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany;Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St., Gallen, Switzerland;Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac, Montpellier, France;

关键词: amyotrophic lateral sclerosis;    disease-modification;    clinical trial protocol;    ROCK inhibition;    study design;   

DOI  :  10.3389/fneur.2019.00293

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown