一项使用真实世界数据评估波舒替尼治疗肌萎缩侧索硬化症的 2 期研究方案：肌萎缩侧索硬化症药物再利用的诱导多能干细胞研究（iDReAM 研究）。
Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study.
机构信息
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
出版信息
BMJ Open. 2024 Oct 26;14(10):e082142. doi: 10.1136/bmjopen-2023-082142.
INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing identified a Src/c-Abl inhibitor, bosutinib, as a candidate for molecular targeted therapy of ALS. A phase 1 study confirmed the safety and tolerability of bosutinib in a 12-week treatment of ALS patients. The objectives of this study are to evaluate the efficacy and longer-term safety of bosutinib in ALS patients.
METHODS AND ANALYSIS
An open-label, multicentre phase 2 study was designed. The study consisted of a 12-week observation period, a 1-week transitional period, a 24-week study treatment period and a 4-week follow-up period. Following the transitional period, patients whose total Revised ALS Functional Rating Scale (ALSFRS-R) score declined by 1 to 4 points during the 12-week observation period were to receive bosutinib for 24 weeks. In this study, 25 ALS patients will be enrolled; patients will be randomly assigned to the following groups: 12 patients in the 200 mg quaque die (QD) group and 13 patients in the 300 mg QD group of bosutinib. The safety and exploratory efficacy of bosutinib in ALS patients for 24 weeks will be assessed. Efficacy using the ALSFRS-R score will be compared with the external published data from an edaravone study (MCI186-19) and registry data from a multicentre ALS cohort study, the Japanese Consortium for Amyotrophic Lateral Sclerosis Research.
ETHICS AND DISSEMINATION
This study was approved by the ethics committees of Kyoto University, Tokushima University, Kitasato University, Tottori University, Nara Medical University School of Medicine, Toho University and Hiroshima University. The findings will be disseminated in peer-reviewed journals and at scientific conferences.
TRIAL REGISTRATION NUMBER
jRCT2051220002; Pre-results, NCT04744532; Pre-results.
简介
肌萎缩侧索硬化症（ALS）是一种由运动神经元死亡引起的进行性、严重的神经退行性疾病。迫切需要开发治疗 ALS 的药物，基于诱导多能干细胞的药物再利用发现Src/c-Abl 抑制剂波舒替尼是 ALS 分子靶向治疗的候选药物。一项 1 期研究证实了波舒替尼在 12 周 ALS 患者治疗中的安全性和耐受性。本研究的目的是评估波舒替尼治疗 ALS 患者的疗效和长期安全性。
方法和分析
本研究设计为开放标签、多中心 2 期研究。该研究包括 12 周观察期、1 周过渡期、24 周研究治疗期和 4 周随访期。在过渡期后，如果患者在 12 周观察期内总修订 ALS 功能评定量表（ALSFRS-R）评分下降 1-4 分，则接受波舒替尼治疗 24 周。本研究将纳入 25 例 ALS 患者；患者将被随机分为以下两组：波舒替尼 200mg 每日两次（QD）组 12 例和 300mg QD 组 13 例。将评估波舒替尼治疗 ALS 患者 24 周的安全性和探索性疗效。使用 ALSFRS-R 评分比较波舒替尼治疗 ALS 患者的疗效与依达拉奉研究（MCI186-19）的外部发表数据和多中心 ALS 队列研究日本肌萎缩侧索硬化症研究联合会的注册数据。
伦理和传播
本研究已获得京都大学、德岛大学、北里大学、鸟取大学、奈良医科大学、东邦大学和广岛大学伦理委员会的批准。研究结果将在同行评议的期刊和科学会议上发表。
试验注册号
jRCT2051220002；预结果，NCT04744532；预结果。
Zotero 插件