Design of phase 2 study of TAS-115, a novel oral multi-kinase inhibitor, in patients with idiopathic pulmonary fibrosis

BACKGROUND: TAS-115, a novel multi-kinase inhibitor, demonstrated antifibrotic effects in vitro and in vivo. METHODS: This is an open-label, intra-patient comparison, exploratory phase 2 study of TAS-115 to evaluate the efficacy and safety in idiopathic pulmonary fibrosis (IPF) patients when orally administered at 200 mg once daily on a 5-day on and 2-day off regimen for 13 weeks. This study consists of three cohorts: previously treated with pirfenidone (Cohort P, n = 20), with nintedanib (Cohort N, n = 20), and treatment naïve (Cohort U, n = 10). Male or female patients aged ≥40 to <80 years who were diagnosed with IPF in the preceding five years and having a percent predicted forced vital capacity (%FVC) decline of ≥5% within the previous 6 months were enrolled in this study. The primary endpoint is change in the slope of %FVC decline at Week 13 from baseline. Key secondary endpoints are safety, change in FVC from baseline, proportion of the %FVC responders and change in percent predicted diffusing capacity of the lung carbon monoxide from baseline, which are assessed at Weeks 6, 13 and 26. RESULTS: Enrollment of 45 patients was completed in July 2019. Results will be reported in 2021. DISCUSSION: This trial is intended to demonstrate the clinical efficacy of TAS-115 in IPF patients who have not responded to pirfenidone or nintedanib, as well as in those who are pirfenidone/nintedanib treatment naïve. The safety and tolerability in this population will be assessed. TRIAL REGISTRATION: JapicCTI-183898.