JMIR Research Protocols (Jan 2023)

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
https://doi.org/10.2196/42032
Journal volume & issue
Vol. 12
p. e42032

Abstract

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BackgroundAmyotrophic 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. ObjectiveThis protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). MethodsEPIC-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. ResultsThis trial began data collection in September 2021 and is expected to be completed in October 2023. ConclusionsThis study can provide useful data to understand the characteristics of EPI-589. Trial RegistrationJapan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6 International Registered Report Identifier (IRRID)DERR1-10.2196/42032