Protocol and rationale for a randomised, double-blind, placebo-controlled phase 3 trial of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with idiopathic pulmonary fibrosis: ALOFT-IPF

Introduction Idiopathic pulmonary fibrosis (IPF) is associated with progressive loss of lung function and poor prognosis. There remains a need for novel therapies for patients with IPF. Admilparant, an oral lysophosphatidic acid receptor 1 antagonist, slowed lung function decline and was well tolerated in a phase 2 trial when administered 60 mg two times per day in patients with IPF over 26 weeks. This report describes the design and rationale of the pivotal ALOFT-IPF phase 3 trial, which aims to further evaluate admilparant for patients with IPF.Methods and analysis ALOFT-IPF, a global, phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trial, completed enrolment on 5 September 2025. Adults (≥40 years) with IPF were randomised to receive admilparant 60 mg or 120 mg or placebo (1:1:1) orally, two times per day for ≥52 weeks. Inclusion criteria included IPF diagnosis within 7 years, percentage of predicted forced vital capacity ≥40% and percentage of predicted diffusing capacity of the lung for carbon monoxide ≥25%. Background antifibrotic treatment was permitted. Randomisation was stratified by antifibrotic therapy and sex. A two-cohort design was used to assess the safety of admilparant 120 mg. Cohort 1 (n=60), a single-blind design, evaluated safety and tolerability of admilparant; the primary endpoint was the number of spontaneous syncopal episodes after 4 weeks. Based on data evaluation, continuation of the trial was permitted without change and recruitment into cohort 2 initiated. Cohort 2 (n=1191) has a registrational, double-blind design to evaluate the efficacy, safety and tolerability of admilparant compared with placebo; the primary endpoint is absolute change in forced vital capacity from baseline at week 52. The trial is estimated to complete in October 2026.Ethics and dissemination This trial is being conducted in accordance with the protocol and international guidelines, applicable local laws, regulations and requirements.Trial registration number NCT06003426.