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

Background: Admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, was well tolerated and associated with reduced lung function decline over 26 weeks compared with placebo in a phase 2 trial for patients with progressive pulmonary fibrosis (PPF) (Corte, 2025, AJRCCM). The ALOFT-PPF phase 3 trial aims to further investigate admilparant in patients with PPF, currently enrolling across>30 countries. Methods: ALOFT-PPF (NCT06025578), a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial, is randomizing adults (≥21 years) with PPF to receive admilparant 60 or 120 mg or placebo (1:1:1) orally, twice daily for≥52 weeks, stratified by background therapy (antifibrotic and/or immunosuppressive therapy or none) and/or usual interstitial pneumonia pattern ([ Fig. 1 ]). Key inclusion criteria are interstitial lung disease diagnosis with progression within 24 months, high-resolution computed tomography≥10% fibrosis, percent of predicted forced vital capacity (ppFVC)≥40%, and percent of predicted diffusing capacity of the lung for carbon monoxide≥25%. Background therapy with antifibrotics and certain immunosuppressives is allowed. ALOFT-PPF included an initial single-blind design cohort 1 (N=25) to evaluate safety of admilparant at 120 mg; the primary endpoint was spontaneous syncopal episodes after 4 weeks. After data evaluation (together with ALOFT-IPF [NCT06003426] data), the double-blind cohort 2 was initiated without change. Cohort 2 (N~1032) evaluates efficacy and safety 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 October 25, 2023, and will continue until the target is reached. Conclusion: ALOFT-PPF will evaluate the effect of admilparant on safety, absolute change in FVC, disease progression and quality-of-life over≥52 weeks in patients with PPF. 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