An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study

Shotaro Haji; Koji Fujita; Ryosuke Oki; Yusuke Osaki; Ryosuke Miyamoto; Hiroyuki Morino; Seiichi Nagano; Naoki Atsuta; Yuki Kanazawa; Yuki Matsumoto; Atsuko Arisawa; Hisashi Kawai; Yasutaka Sato; Satoshi Sakaguchi; Kenta Yagi; Tatsuto Hamatani; Tatsuo Kagimura; Hiroaki Yanagawa; Hideki Mochizuki; Manabu Doyu; Gen Sobue; Masafumi Harada; Yuishin Izumi

doi:10.2196/42032

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study

JMIR Res Protoc. 2023 Jan 30:12:e42032. doi: 10.2196/42032.

Authors

Shotaro Haji¹, Koji Fujita¹, Ryosuke Oki¹, Yusuke Osaki¹, Ryosuke Miyamoto¹, Hiroyuki Morino², Seiichi Nagano^{3

4}, Naoki Atsuta⁵, Yuki Kanazawa⁶, Yuki Matsumoto⁷, Atsuko Arisawa⁸, Hisashi Kawai⁹, Yasutaka Sato¹⁰, Satoshi Sakaguchi¹⁰, Kenta Yagi¹⁰, Tatsuto Hamatani¹¹, Tatsuo Kagimura¹², Hiroaki Yanagawa¹⁰, Hideki Mochizuki⁴, Manabu Doyu⁵, Gen Sobue¹³, Masafumi Harada⁷, Yuishin Izumi¹

Affiliations

¹ Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
² Department of Medical Genetics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
³ Department of Neurotherapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
⁴ Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
⁵ Department of Neurology, Aichi Medical University School of Medicine, Nagakute, Japan.
⁶ Department of Biomedical Information Sciences, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
⁷ Department of Radiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
⁸ Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
⁹ Department of Radiology, Aichi Medical University School of Medicine, Nagakute, Japan.
¹⁰ Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan.
¹¹ Sumitomo Pharma Co, Ltd, Osaka, Japan.
¹² The Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan.
¹³ Aichi Medical University School of Medicine, Nagakute, Japan.

PMID: 36716091
PMCID: PMC9926342
DOI: 10.2196/42032

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent.

Objective: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS).

Methods: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area.

Results: This trial began data collection in September 2021 and is expected to be completed in October 2023.

Conclusions: This study can provide useful data to understand the characteristics of EPI-589.

Trial registration: Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6.

International registered report identifier (irrid): DERR1-10.2196/42032.

Keywords: amyotrophic lateral sclerosis; biomarker; clinical trial; magnetic resonance imaging; oxidative stress.

©Shotaro Haji, Koji Fujita, Ryosuke Oki, Yusuke Osaki, Ryosuke Miyamoto, Hiroyuki Morino, Seiichi Nagano, Naoki Atsuta, Yuki Kanazawa, Yuki Matsumoto, Atsuko Arisawa, Hisashi Kawai, Yasutaka Sato, Satoshi Sakaguchi, Kenta Yagi, Tatsuto Hamatani, Tatsuo Kagimura, Hiroaki Yanagawa, Hideki Mochizuki, Manabu Doyu, Gen Sobue, Masafumi Harada, Yuishin Izumi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.01.2023.