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ID 118866
Author
Haji, Shotaro Tokushima University
Oki, Ryosuke Tokushima University
Nagano, Seiichi Osaka University
Atsuta, Naoki Aichi Medical University
Arisawa, Atsuko Osaka University
Kawai, Hisashi Aichi Medical University
Sato, Yasutaka Tokushima University
Hamatani, Tatsuto Sumitomo Pharma Co, Ltd
Kagimura, Tatsuo Foundation for Biomedical Research and Innovation at Kobe
Mochizuki, Hideki Osaka University
Doyu, Manabu Aichi Medical University
Sobue, Gen Aichi Medical University
Keywords
amyotrophic lateral sclerosis
biomarker
clinical trial
magnetic resonance imaging
oxidative stress
Content Type
Journal Article
Description
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.
Journal Title
JMIR Research Protocols
ISSN
19290748
Publisher
JMIR Publications
Volume
12
Start Page
e42032
Published Date
2023-01-30
Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.
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language
eng
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departments
University Hospital
Medical Sciences