Protocol for a randomized, placebo-controlled, double-blind phase IIa study of the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with Parkinson’s disease (ROCK-PD)

Published on February 14, 2024

BackgroundThe Rho-kinase (ROCK) inhibitor Fasudil has shown symptomatic and disease-modifying effects in Parkinson’s disease (PD) models in vitro and in vivo. In Japan, Fasudil has been approved for the treatment of subarachnoid haemorrhage since 1995 and shows a favourable safety profile.Objectives/designTo investigate the safety, tolerability, and symptomatic efficacy of ROCK-inhibitor Fasudil in comparison to placebo in a randomized, national, multicenter, double-blind phase IIa study in patients with PD.Methods/analysisWe plan to include 75 patients with at least ‘probable’ PD (MDS criteria), Hoehn and Yahr stages 1–3, and age 30–80 years in 13 German study sites. Patients must be non-fluctuating and their response to PD medication must have been stable for 6 weeks. Patients will be randomly allocated to treatment with the oral investigational medicinal product (IMP) containing either Fasudil in two dosages, or placebo, for a total of 22 days. As primary analysis, non-inferiority of low/high dose of Fasudil on the combined endpoint consisting of occurrence of intolerance and/or treatment-related serious adverse events (SAEs) over 22 days will be assessed in a sequential order, starting with the lower dose. Secondary endpoints will include tolerability alone over 22 days and occurrence of treatment-related SAEs (SARs) over 22 and 50 days and will be compared on group level. Additional secondary endpoints include efficacy on motor and non-motor symptoms, measured on established scales, and will be assessed at several timepoints. Biomaterial will be collected to determine pharmacokinetics of Fasudil and its active metabolite, and to evaluate biomarkers of neurodegeneration.Ethics/registration/discussionAfter positive evaluation by the competent authority and the ethics committee, patient recruitment started in the 3rd quarter of 2023. ROCK-PD is registered with Eudra-CT (2021-003879-34) and clinicaltrials.gov (NCT05931575). Results of this trial can pave way for conducting extended-duration studies assessing both symptomatic efficacy and disease-modifying properties of Fasudil.

Read Full Article (External Site)