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An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter,
Shotaro Haji1, Koji Fujita1, Ryosuke Oki1
1Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
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.
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