A110-10 Efficacy, Safety, and Tolerability of Fipaxalparant in Patients With Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2B Study

Abstract Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with an increasing prevalence and significant morbidity. Despite the availability of approved antifibrotic agents, there exists a need for novel treatments that limit disease progression with improved tolerability. In this study, we evaluated the efficacy and safety of fipaxalparant, a selective lysophosphatidic acid receptor 1 antagonist in adult patients with IPF. Methods HARBOR (NCT05032066) was a randomized, double-blind, open-label, placebo-controlled, repeat-dose, multicenter phase 2b study with a 52-week core phase and an optional 52-week extension phase. Patients were stratified based on concomitant use of approved IPF therapy (yes/no) and forced vital capacity percent (FVC%) predicted at baseline (≥70%/70%). Key eligibility criteria included adults with a confirmed IPF, as per the ATS/ERS/JRS/ALAT guidelines, with initial diagnosis made within the past 7 years. The primary endpoint of core phase was the change in FVC% predicted from baseline to Week 52; key secondary endpoint at Week 52 includes proportion of patients with decline in FVC% predicted ≥10%. Safety was assessed. Here we report the data of the core phase. Results A total of 153 patients were randomized (1:1:1) to receive fipaxalparant 300 mg BID (n = 52) or 300 mg QD (n = 49), or placebo (n = 52). Most patients were male (66%) and the mean age (SD) was 71.1 (7.4) years. Least-square mean (SE) change from baseline at Week 52 in FVC% was -3.38 (1.09) in the BID group and -4.13 (1.05) in the QD group, and -2.99 (1.03) in the placebo group, with the placebo-adjusted least-square mean differences of -0.39 (90% CI: -2.86-2.09; P=0.7959) and -1.13 (90% CI: -3.56-1.29; P=0.4388) in the BID and QD groups, respectively (Figure). Overall, 53.8%, 67.3%, and 71.2% of patients receiving BID, QD fipaxalparant, or placebo, respectively, had 10% decline in FVC%. Treatment-emergent adverse events (AEs) and serious AEs occurred in 80.8% and 26.9% of patients in the BID group, 77.6% and 20.4% of patients in the QD group, and 73.1% and 17.3% of patients in the placebo group. Grade ≥3 AEs were reported in 3.8%, 2.0%, and 1.9% of patients in BID, QD, and placebo groups, respectively. Conclusions The FVC% predicted change from baseline at Week 52 for fipaxalparant 300 mg BID or QD did not demonstrate a slowing of lung function decline relative to placebo. The extension phase of this study was terminated due to lack of efficacy and not based on safety concerns. This abstract is funded by: Amgen Inc.