DMD CLINICAL THERAPIES I: P.121Phase II study of TAS-205 in patients with Duchenne muscular dystrophy: subgroup analyses

Abstract

Inflammation has been included in the pathological process of Duchenne muscular dystrophy (DMD). Prostaglandin D2 (PGD2) is produced by various inflammatory cells, and hematopoietic PGD synthase (HPGDS) is shown to be expressed in the necrotic muscles of DMD patients. The primary objective of this study was to evaluate the efficacy of TAS-205, a specific inhibitor of HPGD2S, orally administered twice daily for 24 weeks, compared with placebo in ambulatory DMD patients. For this double-blind study, subjects were evenly randomized to one of the three groups, a low-dose (6.67 to 13.33 mg/kg/dose), high-dose (13.33 to 26.67 mg/kg/dose), or placebo group. A total of 36 subjects were enrolled. The primary endpoint was the change from baseline in the measured 6-minute walk distance (6MWD) at week 24. The mean value difference from the placebo group was 13.5 m for the low-dose group and 9.5 m for the high-dose group. Subgroup analyses of the primary endpoint and secondary endpoints (motor function, muscle volume) were performed with two baseline 6MWD categories, <350 m and ≥350 m. The differences of almost all functional parameters of motor evaluations between the TAS-205 high-dose group and the placebo group tended to be larger in the group with baseline 6MWD ≥350 m than in that with baseline 6MWD <350 m. The muscle volume index (%MVI), evaluated using CT, of the thigh and lower leg significantly decreased at week 24 in the placebo group, which confirmed the reliability of the method. The %MVI reduction of the thigh and lower leg tended to be lower in the TAS-205 group than that in the placebo group. Results of model and correlation analyses in the patients with baseline 6MWD ≥350 m using the alterations of baseline 6MWD and lower leg %MVI at week 24 indicated their relatively high relationship. It was suggested that these data confirm the clinical benefit of TAS-205 in terms of preserving muscle function.