EPI-589治疗肌萎缩侧索硬化症的探索性试验（EPIC-ALS）：一项多中心、开放标签、为期24周的单组研究方案。
An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.
作者信息
Haji Shotaro, Fujita Koji, Oki Ryosuke, Osaki Yusuke, Miyamoto Ryosuke, Morino Hiroyuki, Nagano Seiichi, Atsuta Naoki, Kanazawa Yuki, Matsumoto Yuki, Arisawa Atsuko, Kawai Hisashi, Sato Yasutaka, Sakaguchi Satoshi, Yagi Kenta, Hamatani Tatsuto, Kagimura Tatsuo, Yanagawa Hiroaki, Mochizuki Hideki, Doyu Manabu, Sobue Gen, Harada Masafumi, Izumi Yuishin
机构信息
Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Department of Medical Genetics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
出版信息
JMIR Res Protoc. 2023 Jan 30;12:e42032. doi: 10.2196/42032.
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.
背景
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其目前获批的药物，包括利鲁唑和依达拉奉，治疗效果有限。因此，迫切需要安全有效的药物。EPI-589是一种口服可用的小分子新型氧化还原活性剂，具有对氧化应激的高效保护作用且血脑屏障通透性高。鉴于明显的氧化应激和线粒体功能障碍参与了ALS的发病机制，EPI-589有望成为一种治疗药物。
目的
本方案旨在描述EPI-589用于ALS的2期早期研究者发起的临床试验（EPIC-ALS）的设计和原理。
方法
EPIC-ALS是一项探索性、开放标签、单臂试验，评估EPI-589在ALS患者中的安全性和耐受性。该试验包括12周的导入期、24周的治疗期和4周的随访期。在24周的治疗期内，患者将每天3次接受500 mg的EPI-589。临床评估包括肌萎缩侧索硬化症功能评定量表修订版总分的平均每月变化。选择生物标志物以分析对氧化应激和神经元损伤的影响。血浆生物标志物为8-羟基-2'-脱氧鸟苷（8-OHdG）、3-硝基酪氨酸（3-NT）、神经丝轻链（NfL）、磷酸化神经丝重链（pNfH）、同型半胱氨酸和肌酐。脑脊液生物标志物为8-OHdG、3-NT、NfL、pNfH和鸟氨酸。磁共振生物标志物为皮质脊髓束的分数各向异性和初级运动区的N-乙酰天门冬氨酸。
结果
该试验于2021年9月开始数据收集，预计于2023年10月完成。
结论
本研究可为了解EPI-589的特性提供有用数据。
试验注册
日本初级注册网络jRCT2061210031；tinyurl.com/2p84emu6。
国际注册报告识别码（IRRID）：DERR1-10.2196/42032。
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