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
13 affiliations
- 1National Heart and Lung Institute, Imperial College London, London, UK
- 2Royal Prince Alfred Hospital and University of Sydney, Sydney, New South Wales, Australia
- 35University of Colorado School of Medicine, Denver, Colorado, United States of America
- 4Lung Center Mainz, University Medical Center, Mainz and Marienhaus Clinic Mainz, Mainz, Germany
- 5National Reference Centre for Rare Pulmonary Diseases (Orphalung), Louis Pradel Hospital, Lyon, France
- 6Department of Oncology, Chengdu BOE Hospital, Chengdu, Sichuan, China
- 7Department of Respiratory Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
- 8University of Massachusetts Chan Medical School/UMass Memorial Health System, Worcester, Massachusetts, USA
- 9Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
- 10Peking Union Medical College Hospital, Beijing, China
- 11Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
- 12Department of Conservative Dentistry and Endodontics, Datta Meghe Institute of Higher Education and Research Deemed to be University, Wardha, India
- 13Bristol Myers Squibb, Princeton, New Jersey, USA
Abstract
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.
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BibTeX
@article{maher2026protocol,
title = {{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}},
author = {Toby M Maher and Tamera J Corte and Aryeh Fischer and Michael Kreuter and Vincent Cottin and Yue Wang and Marlies Wijsenbeek and Fernando Martinez and Takafumi Suda and Zuojun Xu and Takashi Ogura and Aditya Patel and Elizabeth Cerullo and Walid Elsharkawi},
journal = {BMJ Open Respiratory Research},
year = {2026},
month = oct,
doi = {10.1136/bmjresp-2026-004324},
url = {https://doi.org/10.1136/bmjresp-2026-004324},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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
AU - Toby M Maher
AU - Tamera J Corte
AU - Aryeh Fischer
AU - Michael Kreuter
AU - Vincent Cottin
AU - Yue Wang
AU - Marlies Wijsenbeek
AU - Fernando Martinez
AU - Takafumi Suda
AU - Zuojun Xu
AU - Takashi Ogura
AU - Aditya Patel
AU - Elizabeth Cerullo
AU - Walid Elsharkawi
PY - 2026
DA - 2026/10/23
JO - BMJ Open Respiratory Research
DO - 10.1136/bmjresp-2026-004324
UR - https://doi.org/10.1136/bmjresp-2026-004324
AB - 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.
SN - 2052-4439
ER -