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. 2024 Oct 26;14(10):e082142.
doi: 10.1136/bmjopen-2023-082142.

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

Keiko Imamura  1 , Yuishin Izumi  2 , Naohiro Egawa  3 , Takashi Ayaki  3 , Makiko Nagai  4 , Kazutoshi Nishiyama  4 , Yasuhiro Watanabe  5 , Takenobu Murakami  5 , Ritsuko Hanajima  5 , Hiroshi Kataoka  6 , Takao Kiriyama  6 , Hitoki Nanaura  6 , Kazuma Sugie  6 , Takehisa Hirayama  7 , Osamu Kano  7 , Masahiro Nakamori  8 , Hirofumi Maruyama  8 , Shotaro Haji  2 , Koji Fujita  2 , Naoki Atsuta  9 , Harutsugu Tatebe  10 , Takahiko Tokuda  10 , Naoto Takahashi  11 , Akiko Morinaga  12 , Riko Tabuchi  13 , Motoki Oe  13 , Mihoko Kobayashi  13 , Kasia Lobello  14 , Satoshi Morita  15   16 , Gen Sobue  17 , Ryosuke Takahashi  3 , Haruhisa Inoue  18   16
Affiliations

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

Keiko Imamura et al. BMJ Open. .

Abstract

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.

Keywords: Clinical trials; NEUROLOGY; REGISTRIES.

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Conflict of interest statement

Competing interests: Kyoto University is the study sponsor. The study drug bosutinib and the pharmacokinetic analysis for only patient-experienced serious adverse events are supported by Pfizer JAPAN INC. under the Clinical Research Collaboration Agreement between Kyoto University and Pfizer JAPAN INC. RTak and NT received research funding and honoraria for lectures from Pfizer.

Figures

Figure 1
Figure 1. Schema of study design.
See this image and copyright information in PMC

References

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    1. Imamura K, Izumi Y, Banno H, et al. Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients. BMJ Open. 2019;9:e033131. doi: 10.1136/bmjopen-2019-033131. - DOI - PMC - PubMed
    1. Imamura K, Izumi Y, Nagai M, et al. Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial. EClinMed. 2022;53:101707. doi: 10.1016/j.eclinm.2022.101707. - DOI - PMC - PubMed

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