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

Background: Approved antifibrotics for idiopathic pulmonary fibrosis (IPF) slow lung function decline but do not halt disease progression and are poorly tolerated. In a phase 2 trial, admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, slowed lung function decline and was well tolerated in patients with IPF (Corte, 2025, AJRCCM). The ALOFT-IPF phase 3 trial aims to further evaluate admilparant for patients with IPF, enrolling across>30 countries. Methods: ALOFT-IPF (NCT06003426), a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, is randomizing adults (≥40 years) with IPF to receive admilparant 60 or 120 mg or placebo (1:1:1) orally, twice daily for≥52 weeks, stratified by antifibrotic therapy (nintedanib vs pirfenidone vs none) and sex. Inclusion criteria include IPF diagnosis within 7 years, percent of predicted forced vital capacity (ppFVC)≥40%, and percent of predicted diffusing capacity of the lung for carbon monoxide≥25%. Background antifibrotic treatment is permitted. ALOFT-IPF uses a 2-cohort design ([ Fig. 1 ]). Cohort 1 (N=60), a single-blind design, evaluated the safety and tolerability of admilparant; the primary endpoint was the number of spontaneous syncopal episodes (admilparant 120 mg vs placebo) after 4 weeks. Based on data evaluation, continuation of the trial was permitted without change, and recruitment into cohort 2 initiated. Cohort 2 (N~1125) has a registrational, double-blind design to evaluate efficacy, safety, and tolerability of admilparant compared with placebo; the primary endpoint is absolute change in FVC from baseline to week 52. Key secondary endpoints include time to disease progression (absolute ppFVC decline≥10%, acute exacerbation of pulmonary fibrosis, respiratory-related hospitalizations, and all-cause mortality), change from baseline to week 52 in the Living with Pulmonary Fibrosis (L-PF) questionnaire cough domain score, 6-minute walking distance, and L-PF dyspnea domain score. Results: Enrollment began on September 14, 2023, and was completed on September 5, 2025. Conclusion: ALOFT-IPF will determine the effect of admilparant on safety, absolute change in FVC, disease progression, and quality of life over≥52 weeks in patients with IPF. Fig. 1 Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany