2. Academic Validation
  3. Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy

Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy

  • Ann Clin Transl Neurol. 2020 Feb;7(2):181-190. doi: 10.1002/acn3.50978.
Hirofumi Komaki 1,  Yoshihiro Maegaki 2,  Tsuyoshi Matsumura 3,  Kazuhiro Shiraishi 4,  Hiroyuki Awano 5,  Akinori Nakamura 6,  Satoru Kinoshita 7,  Katsuhisa Ogata 8,  Keiko Ishigaki 9,  Shinji Saitoh 10,  Michinori Funato 11,  Satoshi Kuru 12,  Takahiro Nakayama 13,  Yasuyuki Iwata 14,  Hiroyuki Yajima 14,  Shin'ichi Takeda 15
Affiliations

Affiliations

  • 1 Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • 2 Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Tottori, Japan.
  • 3 Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Osaka, Japan.
  • 4 Department of Pediatrics, National Hospital Organization Utano National Hospital, Kyoto, Japan.
  • 5 Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan.
  • 6 Third Department of Medicine, Shinshu University School of Medicine, Nagano, Japan.
  • 7 Department of Pediatrics, National Hospital Organization Niigata National Hospital, Niigata, Japan.
  • 8 Department of Neurology, National Hospital Organization Higashisaitama National Hospital, Saitama, Japan.
  • 9 Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
  • 10 Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
  • 11 Department of Pediatrics, National Hospital Organization Nagara Medical Center, Gifu, Japan.
  • 12 Department of Neurology, National Hospital Organization Suzuka National Hospital, Mie, Japan.
  • 13 Department of Neurology, Division of Neuromuscular diseases, Yokohama Rosai Hospital, Kanagawa, Japan.
  • 14 Department of Rehabilitation, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • 15 National Center of Neurology and Psychiatry, Tokyo, Japan.
PMID: 31957953 DOI: 10.1002/acn3.50978
Abstract

Objective: Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D2 (PGD2 ) 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.

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