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)

Satoshi Suda, Chikako Nito, Masafumi Ihara, Yasuyuki Iguchi, Takao Urabe, Yuji Matsumaru, Nobuyuki Sakai, Kazumi Kimura, J- REPAIR trial group, Seiji Okubo, Masataka Takeuchi, Masaki Takao, Shinichi Takahashi, Masafumi Morimoto, Yasuhisa Akaiwa, Norihiro Ishii, Takao Kanzawa, Mitsuyasu Kanai, Shinichi Yoshimura, Hideo Hara, Akira Tsujino, Eiichiro Kamatsuka, Takeshi Inoue, Takeshi Iwanaga, Yuka Terasawa, Ryuzaburo Kanazawa, Masahiro Yasaka, Kenichi Morita, Norimichi Nakamura, Takeshi Yoshimoto, Yutaka Honma, Taketo Hatano, Tomohiko Izumidani, Shoji Arihiro, Takayuki Mizunari, Satoshi Suda, Chikako Nito, Masafumi Ihara, Yasuyuki Iguchi, Takao Urabe, Yuji Matsumaru, Nobuyuki Sakai, Kazumi Kimura, J- REPAIR trial group, Seiji Okubo, Masataka Takeuchi, Masaki Takao, Shinichi Takahashi, Masafumi Morimoto, Yasuhisa Akaiwa, Norihiro Ishii, Takao Kanzawa, Mitsuyasu Kanai, Shinichi Yoshimura, Hideo Hara, Akira Tsujino, Eiichiro Kamatsuka, Takeshi Inoue, Takeshi Iwanaga, Yuka Terasawa, Ryuzaburo Kanazawa, Masahiro Yasaka, Kenichi Morita, Norimichi Nakamura, Takeshi Yoshimoto, Yutaka Honma, Taketo Hatano, Tomohiko Izumidani, Shoji Arihiro, Takayuki Mizunari

Abstract

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.

Keywords: INTERNAL MEDICINE; NEUROLOGY; Neurology; Stroke.

Conflict of interest statement

Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Expert Witness from Teijin Pharma Ltd. (SS, CN, KK). Research funding from Teijin Pharma Ltd. (KK). Lecture fee from Teijin Pharma Ltd. (YI). The other authors report no conflicts.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of the cohorts. DSMB, Data and Safety Monitoring Board.

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