Abstract Details

Title Phase 1/2a, Double-blind, Placebo-controlled Study of Ropinirole Hydrochloride Remedy for ALS (ROPALS trial) Based On The iPSC Drug Repositioning

Topic General Neurology

Presentation(s) General Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 096

Objective

In December 2018, we started an investigator-initiated clinical trial (UMIN000034954, JMA-IIA00397) testing ropinirole hydrochloride for amyotrophic lateral sclerosis (ALS). The aims are to assess the safety and tolerability as well as efficacy of ropinirole hydrochloride in patients with ALS.

Background

No effective treatment has been established for ALS because of a limitation of animal model for drug development. Thus, we performed drug screening using motor neurons (MNs) derived from disease-specific-induced pluripotent stem cells (iPSC) for ALS and we found that ropinirole hydrochloride inhibited reactive oxygen species and the abnormal aggregation of TDP-43 or FUS, improved mitochondrial function, and prevented MN death (Fujimori K, et al. Nat Med 2018).

Design/Methods This is a phase I/IIa randomized, double-blind, placebo-controlled, single-center (Keio University, Japan), open-label continuation clinical trial (Morimoto S, et al. Regen Ther 2019). The major inclusion criteria were: 1) "clinically possible and laboratory-supported ALS", "clinically probable ALS" or "clinically definite ALS" according to the criteria for the diagnosis of ALS (El Escorial revised) and within 60 months after disease onset; 2) each ALSFRS-R score ?2 points; 3) change in total ALSFRS-R score of -2 to -5 points during the 12-week run-in period. The primary aim is to assess the safety and tolerability of ropinirole hydrochloride. Secondary outcomes include: Combined Assessment of Function and Survival (CAFS), ALSFRS-R score, quantitative muscle strength and volume, and an efficacy evaluation using subjects-derived iPSCs/MNs.

Results

A total of 29 patients have been recruited; 21 of these patients (13 men) are enrolled in the 24-week double-blind phase. At enrollment, the mean±SD disease duration was 20±11 months. ALSFRS-R score was 40±3 (3±1 reduction during the run-in period). The whole trial was completed in July 2020 and the results will be known by April 2021.

Conclusions

Our trial will be a touchstone trial for iPSC-based drug repositioning and will provide promising data.

Authors/Disclosures
Shinichi Takahashi, MD (Saitama med univ International med ctr, Neurology and Stroke) PRESENTER	The institution of Dr. Takahashi has received research support from JSPS KAKENHI. The institution of Dr. Takahashi has received research support from Eisai Japan. The institution of Dr. Takahashi has received research support from Bayer Japan. The institution of Dr. Takahashi has received research support from Boehringer Ingelheim Japan.
Satoru Morimoto	Satoru Morimoto has nothing to disclose.
	No disclosure on file
Yugaku Date, MD, PhD (Saiseikai Yokohama City Eastern Hospital)	Dr. Daté has nothing to disclose.
	No disclosure on file
Jin Nakahara, MD, PhD, FAAN (Keio University School of Medicine)	Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Chugai. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Japanese Society for Internal Medicine. The institution of Prof. Nakahara has received research support from Chugai. The institution of Prof. Nakahara has received research support from Japan Society for the Promotion of Science.
	No disclosure on file

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