Open AccessEarly phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy
Author(s) -
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
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.50978
Subject(s) - medicine , duchenne muscular dystrophy , placebo , adverse effect , clinical endpoint , muscular dystrophy , randomized controlled trial , gastroenterology , pathology , alternative medicine
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.