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- Title
An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.
- Authors
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
- 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.
- Subjects
AMYOTROPHIC lateral sclerosis; NEURODEGENERATION; EDARAVONE; RILUZOLE; OXIDATIVE stress; BLOOD-brain barrier
- Publication
JMIR Research Protocols, 2023, Vol 12, Issue 1, p819
- ISSN
1929-0748
- Publication type
Article
- DOI
10.2196/42032