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)
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-...
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2022-05-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Hideo Hara |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4bd69d43a57e478bb7ce85b76fd06260 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-4bd69d43a57e478bb7ce85b76fd062602025-08-20T02:16:55ZengBMJ Publishing GroupBMJ Open2044-60552022-05-0112510.1136/bmjopen-2021-054269Randomised 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 HaraNobuyuki Sakai0Shinichi Yoshimura1Masafumi Ihara2Satoshi Suda3Chikako Nito4Kazumi Kimura5Yuji Matsumaru6Taketo Hatano7Masaki Takao8Takeshi YoshimotoMasahiro Yasaka9Masafumi Morimoto10Akira TsujinoTakeshi InoueSeiji OkuboMitsuyasu Kanai11Kenichi MoritaYuka TerasawaYasuyuki Iguchi12Takao Urabe13Masataka TakeuchiShinichi Takahashi14Yasuhisa AkaiwaNorihiro IshiiTakao KanzawaEiichiro KamatsukaTakeshi IwanagaRyuzaburo KanazawaNorimichi NakamuraYutaka Honma15Tomohiko IzumidaniShoji ArihiroTakayuki MizunariNeurovascular Research, Kobe City Medical Center General Hospital, Kobe, JapanNeurosurgery, Hyogo Medical University, Nishinomiya, JapanDepartment of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan1 Department of Neurology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan1 Department of Neurology, Nippon Medical School, Bunkyo-ku, Tokyo, JapanDepartment of Neurology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, JapanNeurosurgery, University of Tsukuba, Tsukuba, Japan5 Neurosurgery, Kokura Memorial Hospital, Kitakyushu, Fukuoka, JapanDepartment of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, JapanNational Hospital Organization Kyushu Medical Center, Fukuoka, Japan3 Neurosurgery, Yokohama Shintoshi Neurosurgical Hospital, Yokohama, Kanagawa, Japan8 Department of Neurology, National Hospital Organization Takasaki General Medical Center, Gunma, Japan3 Department of Neurology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan4 Department of Neurology, Juntendo University Urayasu Hospital, Urayasu, Chiba, JapanDepartment of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama, JapanDepartment of Neurology, Showa General Hospital, Kodaira, JapanIntroduction 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.https://bmjopen.bmj.com/content/12/5/e054269.full |
| spellingShingle | 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 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) BMJ Open |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/12/5/e054269.full |
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