Exploratory phase 2 study of the novel oral multi-kinase inhibitor TAS-115 in patients with idiopathic pulmonary fibrosis

• Published in: Respiratory investigation 2023-07, Vol.61 (4), p.498-507
• Main Authors: Nishioka, Yasuhiko, Homma, Sakae, Ogura, Takashi, Sato, Seidai, Arai, Naoki, Tomii, Keisuke, Kamio, Koichiro, Sakamoto, Susumu, Miyazaki, Yasunari, Tomioka, Hiromi, Hisata, Shu, Handa, Tomohiro, Azuma, Arata
• Format: Article
• Language: English
• Subjects: Clinical trial; Forced vital capacity; Idiopathic pulmonary fibrosis; Multi-kinase inhibitor; Phase 2
• ISSN: 2212-5345; 2212-5353
• DOI: 10.1016/j.resinv.2023.04.008

TAS-115, a novel oral multi-kinase inhibitor, showed antifibrotic effects in in vitro and in vivo animal models of idiopathic pulmonary fibrosis (IPF). In this exploratory phase 2 study, IPF patients with a percent predicted forced vital capacity (%FVC) decline ≥5% acquired within the previous 6 months were enrolled. Patients were divided into three pre-treatment cohorts, namely, treatment-naïve, pirfenidone, or nintedanib. TAS-115 was administered orally at 200 mg/day with a 5-day on and 2-day off regimen. After 13 weeks of treatment, patients entered a 13-week extension treatment period where the efficacy was evaluated. The primary endpoint was the difference in slope of %FVC decline at Week 13 from baseline. Safety was also evaluated. Between June 2018 and July 2019, 46 patients were enrolled, and 30 (65.2%) patients completed the 13-week treatment. Of these, 22 (47.8%) proceeded to extension treatment. For the primary endpoint, TAS-115 treatment lowered the slope of the %FVC decline of 0.0750%/day (95% confidence interval: 0.0341–0.1158%/day) at Week 13. Efficacy was also demonstrated at Week 26. Treatment-related adverse events were reported in 40 (88.9%) patients, but most were manageable by dose reduction, dose interruption, or symptomatic treatment. TAS-115 treatment was effective, assessed using intra-patient change in slope of %FVC decline as a surrogate endpoint in patients with IPF pre-treated with pirfenidone or nintedanib and treatment-naïve patients. TAS-115 showed acceptable tolerability and a manageable safety profile. Japic-Clinical Trials Information, JapicCTI-183898 (first registered: March 15, 2018).