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Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy
OBJECTIVE: Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D(2) (PGD(2)) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034509/ https://www.ncbi.nlm.nih.gov/pubmed/31957953 http://dx.doi.org/10.1002/acn3.50978 |
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author | Komaki, Hirofumi Maegaki, Yoshihiro Matsumura, Tsuyoshi Shiraishi, Kazuhiro Awano, Hiroyuki Nakamura, Akinori Kinoshita, Satoru Ogata, Katsuhisa Ishigaki, Keiko Saitoh, Shinji Funato, Michinori Kuru, Satoshi Nakayama, Takahiro Iwata, Yasuyuki Yajima, Hiroyuki Takeda, Shin’ichi |
author_facet | Komaki, Hirofumi Maegaki, Yoshihiro Matsumura, Tsuyoshi Shiraishi, Kazuhiro Awano, Hiroyuki Nakamura, Akinori Kinoshita, Satoru Ogata, Katsuhisa Ishigaki, Keiko Saitoh, Shinji Funato, Michinori Kuru, Satoshi Nakayama, Takahiro Iwata, Yasuyuki Yajima, Hiroyuki Takeda, Shin’ichi |
author_sort | Komaki, Hirofumi |
collection | PubMed |
description | OBJECTIVE: Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D(2) (PGD(2)) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized, double‐blind, placebo‐controlled early phase 2 study (NCT02752048) aimed to assess the efficacy and safety of the novel selective HPGDS inhibitor, TAS‐205, with exploratory measures in male DMD patients aged ≥5 years. METHODS: Patients were randomized 1:1:1 to receive low‐dose TAS‐205 (6.67–13.33 mg/kg/dose), high‐dose TAS‐205 (13.33–26.67 mg/kg/dose), or placebo. The primary endpoint was the change from baseline in a 6‐minute walk distance (6MWD) at Week 24. RESULTS: Thirty‐six patients were enrolled, of whom 35 patients were analysed for safety. The mean (standard error) changes from baseline to Week 24 in 6MWD were −17.0 (17.6) m in the placebo group (n = 10), −3.5 (20.3) m in the TAS‐205 low‐dose group (n = 11), and −7.5 (11.2) m in the TAS‐205 high‐dose group (n = 11). The mean (95% confidence interval) difference from the placebo group was 13.5 (−43.3 to 70.2) m in the TAS‐205 low‐dose group and 9.5 (−33.3 to 52.4) m in the TAS‐205 high‐dose group. No obvious differences were observed in the incidences of adverse events between treatment groups. No adverse drug reactions specific to TAS‐205 treatment were observed. INTERPRETATION: The HPGDS inhibitor TAS‐205 showed a favorable safety profile in DMD patients. Further research is required to examine the effectiveness of TAS‐205 in a larger trial. |
format | Online Article Text |
id | pubmed-7034509 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70345092020-02-27 Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy Komaki, Hirofumi Maegaki, Yoshihiro Matsumura, Tsuyoshi Shiraishi, Kazuhiro Awano, Hiroyuki Nakamura, Akinori Kinoshita, Satoru Ogata, Katsuhisa Ishigaki, Keiko Saitoh, Shinji Funato, Michinori Kuru, Satoshi Nakayama, Takahiro Iwata, Yasuyuki Yajima, Hiroyuki Takeda, Shin’ichi Ann Clin Transl Neurol Research Articles OBJECTIVE: Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D(2) (PGD(2)) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized, double‐blind, placebo‐controlled early phase 2 study (NCT02752048) aimed to assess the efficacy and safety of the novel selective HPGDS inhibitor, TAS‐205, with exploratory measures in male DMD patients aged ≥5 years. METHODS: Patients were randomized 1:1:1 to receive low‐dose TAS‐205 (6.67–13.33 mg/kg/dose), high‐dose TAS‐205 (13.33–26.67 mg/kg/dose), or placebo. The primary endpoint was the change from baseline in a 6‐minute walk distance (6MWD) at Week 24. RESULTS: Thirty‐six patients were enrolled, of whom 35 patients were analysed for safety. The mean (standard error) changes from baseline to Week 24 in 6MWD were −17.0 (17.6) m in the placebo group (n = 10), −3.5 (20.3) m in the TAS‐205 low‐dose group (n = 11), and −7.5 (11.2) m in the TAS‐205 high‐dose group (n = 11). The mean (95% confidence interval) difference from the placebo group was 13.5 (−43.3 to 70.2) m in the TAS‐205 low‐dose group and 9.5 (−33.3 to 52.4) m in the TAS‐205 high‐dose group. No obvious differences were observed in the incidences of adverse events between treatment groups. No adverse drug reactions specific to TAS‐205 treatment were observed. INTERPRETATION: The HPGDS inhibitor TAS‐205 showed a favorable safety profile in DMD patients. Further research is required to examine the effectiveness of TAS‐205 in a larger trial. John Wiley and Sons Inc. 2020-01-20 /pmc/articles/PMC7034509/ /pubmed/31957953 http://dx.doi.org/10.1002/acn3.50978 Text en © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Komaki, Hirofumi Maegaki, Yoshihiro Matsumura, Tsuyoshi Shiraishi, Kazuhiro Awano, Hiroyuki Nakamura, Akinori Kinoshita, Satoru Ogata, Katsuhisa Ishigaki, Keiko Saitoh, Shinji Funato, Michinori Kuru, Satoshi Nakayama, Takahiro Iwata, Yasuyuki Yajima, Hiroyuki Takeda, Shin’ichi Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title | Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title_full | Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title_fullStr | Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title_full_unstemmed | Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title_short | Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy |
title_sort | early phase 2 trial of tas‐205 in patients with duchenne muscular dystrophy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034509/ https://www.ncbi.nlm.nih.gov/pubmed/31957953 http://dx.doi.org/10.1002/acn3.50978 |
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