Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161, allogeneic human dental pulp stem cells, in patients with Acute Ischaemic stRoke (J-REPAIR)
Hideo Hara,
Nobuyuki Sakai,
Shinichi Yoshimura,
Masafumi Ihara,
Satoshi Suda,
Chikako Nito,
Kazumi Kimura,
Yuji Matsumaru,
Taketo Hatano,
Masaki Takao,
Takeshi Yoshimoto,
Masahiro Yasaka,
Masafumi Morimoto,
Akira Tsujino,
Takeshi Inoue,
Seiji Okubo,
Mitsuyasu Kanai,
Kenichi Morita,
Yuka Terasawa,
Yasuyuki Iguchi,
Takao Urabe,
Masataka Takeuchi,
Shinichi Takahashi,
Yasuhisa Akaiwa,
Norihiro Ishii,
Takao Kanzawa,
Eiichiro Kamatsuka,
Takeshi Iwanaga,
Ryuzaburo Kanazawa,
Norimichi Nakamura,
Yutaka Honma,
Tomohiko Izumidani,
Shoji Arihiro,
Takayuki Mizunari
Affiliations
Hideo Hara
Nobuyuki Sakai
Neurovascular Research, Kobe City Medical Center General Hospital, Kobe, Japan
Shinichi Yoshimura
Neurosurgery, Hyogo Medical University, Nishinomiya, Japan
Masafumi Ihara
Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan
Satoshi Suda
1 Department of Neurology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
Chikako Nito
1 Department of Neurology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
Kazumi Kimura
Department of Neurology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Japan
Yuji Matsumaru
Neurosurgery, University of Tsukuba, Tsukuba, Japan
Taketo Hatano
5 Neurosurgery, Kokura Memorial Hospital, Kitakyushu, Fukuoka, Japan
Masaki Takao
Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
Takeshi Yoshimoto
Masahiro Yasaka
National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
Masafumi Morimoto
3 Neurosurgery, Yokohama Shintoshi Neurosurgical Hospital, Yokohama, Kanagawa, Japan
Akira Tsujino
Takeshi Inoue
Seiji Okubo
Mitsuyasu Kanai
8 Department of Neurology, National Hospital Organization Takasaki General Medical Center, Gunma, Japan
Kenichi Morita
Yuka Terasawa
Yasuyuki Iguchi
3 Department of Neurology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan
Takao Urabe
4 Department of Neurology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
Masataka Takeuchi
Shinichi Takahashi
Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
Yasuhisa Akaiwa
Norihiro Ishii
Takao Kanzawa
Eiichiro Kamatsuka
Takeshi Iwanaga
Ryuzaburo Kanazawa
Norimichi Nakamura
Yutaka Honma
Department of Neurology, Showa General Hospital, Kodaira, Japan
Introduction JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset.Methods and analysis This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5–20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95.Ethics and dissemination The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal.Trial registration number NCT04608838; JapicCTI-194570 and Clinical Trials. gov.
