PMID- 36716091
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230217
IS  - 1929-0748 (Print)
IS  - 1929-0748 (Electronic)
IS  - 1929-0748 (Linking)
VI  - 12
DP  - 2023 Jan 30
TI  - An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): 
      Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.
PG  - e42032
LID - 10.2196/42032 [doi]
LID - e42032
AB  - 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.
CI  - (c)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.
FAU - Haji, Shotaro
AU  - Haji S
AUID- ORCID: 0000-0003-4768-0317
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Fujita, Koji
AU  - Fujita K
AUID- ORCID: 0000-0003-4789-1579
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Oki, Ryosuke
AU  - Oki R
AUID- ORCID: 0000-0002-8017-7863
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Osaki, Yusuke
AU  - Osaki Y
AUID- ORCID: 0000-0001-6588-5442
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Miyamoto, Ryosuke
AU  - Miyamoto R
AUID- ORCID: 0000-0001-6434-9541
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Morino, Hiroyuki
AU  - Morino H
AUID- ORCID: 0000-0002-5190-3547
AD  - Department of Medical Genetics, Tokushima University Graduate School of 
      Biomedical Sciences, Tokushima, Japan.
FAU - Nagano, Seiichi
AU  - Nagano S
AUID- ORCID: 0000-0002-0826-177X
AD  - Department of Neurotherapeutics, Osaka University Graduate School of Medicine, 
      Suita, Japan.
AD  - Department of Neurology, Osaka University Graduate School of Medicine, Suita, 
      Japan.
FAU - Atsuta, Naoki
AU  - Atsuta N
AUID- ORCID: 0000-0002-4911-2690
AD  - Department of Neurology, Aichi Medical University School of Medicine, Nagakute, 
      Japan.
FAU - Kanazawa, Yuki
AU  - Kanazawa Y
AUID- ORCID: 0000-0002-7960-8582
AD  - Department of Biomedical Information Sciences, Tokushima University Graduate 
      School of Biomedical Sciences, Tokushima, Japan.
FAU - Matsumoto, Yuki
AU  - Matsumoto Y
AUID- ORCID: 0000-0002-8369-9237
AD  - Department of Radiology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Arisawa, Atsuko
AU  - Arisawa A
AUID- ORCID: 0000-0003-0773-1263
AD  - Department of Diagnostic and Interventional Radiology, Osaka University Graduate 
      School of Medicine, Suita, Japan.
FAU - Kawai, Hisashi
AU  - Kawai H
AUID- ORCID: 0000-0003-3789-4055
AD  - Department of Radiology, Aichi Medical University School of Medicine, Nagakute, 
      Japan.
FAU - Sato, Yasutaka
AU  - Sato Y
AUID- ORCID: 0000-0001-8179-2211
AD  - Clinical Research Center for Developmental Therapeutics, Tokushima University 
      Hospital, Tokushima, Japan.
FAU - Sakaguchi, Satoshi
AU  - Sakaguchi S
AUID- ORCID: 0000-0002-8916-636X
AD  - Clinical Research Center for Developmental Therapeutics, Tokushima University 
      Hospital, Tokushima, Japan.
FAU - Yagi, Kenta
AU  - Yagi K
AUID- ORCID: 0000-0003-0869-5786
AD  - Clinical Research Center for Developmental Therapeutics, Tokushima University 
      Hospital, Tokushima, Japan.
FAU - Hamatani, Tatsuto
AU  - Hamatani T
AUID- ORCID: 0000-0002-9555-6057
AD  - Sumitomo Pharma Co, Ltd, Osaka, Japan.
FAU - Kagimura, Tatsuo
AU  - Kagimura T
AUID- ORCID: 0000-0001-9856-1006
AD  - The Translational Research Center for Medical Innovation, Foundation for 
      Biomedical Research and Innovation at Kobe, Kobe, Japan.
FAU - Yanagawa, Hiroaki
AU  - Yanagawa H
AUID- ORCID: 0000-0002-6734-2262
AD  - Clinical Research Center for Developmental Therapeutics, Tokushima University 
      Hospital, Tokushima, Japan.
FAU - Mochizuki, Hideki
AU  - Mochizuki H
AUID- ORCID: 0000-0002-0874-7542
AD  - Department of Neurology, Osaka University Graduate School of Medicine, Suita, 
      Japan.
FAU - Doyu, Manabu
AU  - Doyu M
AUID- ORCID: 0000-0002-6264-9927
AD  - Department of Neurology, Aichi Medical University School of Medicine, Nagakute, 
      Japan.
FAU - Sobue, Gen
AU  - Sobue G
AUID- ORCID: 0000-0003-4769-5922
AD  - Aichi Medical University School of Medicine, Nagakute, Japan.
FAU - Harada, Masafumi
AU  - Harada M
AUID- ORCID: 0000-0003-0958-1094
AD  - Department of Radiology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Izumi, Yuishin
AU  - Izumi Y
AUID- ORCID: 0000-0002-3048-9041
AD  - Department of Neurology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230130
PL  - Canada
TA  - JMIR Res Protoc
JT  - JMIR research protocols
JID - 101599504
PMC - PMC9926342
OTO - NOTNLM
OT  - amyotrophic lateral sclerosis
OT  - biomarker
OT  - clinical trial
OT  - magnetic resonance imaging
OT  - oxidative stress
COIS- Conflicts of Interest: TH is an employee of Sumitomo Pharma Co, Ltd.
EDAT- 2023/01/31 06:00
MHDA- 2023/01/31 06:01
PMCR- 2023/01/30
CRDT- 2023/01/30 11:53
PHST- 2022/08/24 00:00 [received]
PHST- 2022/12/08 00:00 [accepted]
PHST- 2022/11/20 00:00 [revised]
PHST- 2023/01/30 11:53 [entrez]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/01/31 06:01 [medline]
PHST- 2023/01/30 00:00 [pmc-release]
AID - v12i1e42032 [pii]
AID - 10.2196/42032 [doi]
PST - epublish
SO  - JMIR Res Protoc. 2023 Jan 30;12:e42032. doi: 10.2196/42032.