Corte Tamera J, Behr Juergen, Cottin Vincent, Glassberg Marilyn K, Kreuter Michael, Martinez Fernando J, Ogura Takashi, Suda Takafumi, Wijsenbeek Marlies, Berkowitz Elchonon, Elpers Brandon, Kim Sinae, Watanabe Hideaki, Fischer Aryeh, Maher Toby M
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
University of Sydney, Sydney, Australia.
Am J Respir Crit Care Med. 2025 Feb;211(2):230-238. doi: 10.1164/rccm.202405-0977OC.
Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF ( = 278 randomized, = 276 treated) or PPF ( = 125 randomized, = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted. Rates of change in percentage of predicted FVC over 26 weeks for IPF were -2.7% (placebo), -2.8% (30 mg), and -1.2% (60 mg) and for PPF were -4.3% (placebo), -2.9% (30 mg), and -1.1% (60 mg). Treatment differences between 60-mg admilparant and placebo were 1.4% (95% confidence interval, -0.1 to 3.0) for IPF and 3.2% (95% confidence interval, 0.7 to 5.7) for PPF. Treatment effect was observed with or without background antifibrotics in both cohorts. Diarrhea occurred at similar frequencies in admilparant arms versus placebo. Transient Day 1 postdose blood pressure reductions were observed in all arms in both cohorts but were greater with admilparant. Treatment discontinuations because of adverse events were similar across IPF arms and lower with admilparant (2.5% [30 mg]; 0% [60 mg]) versus placebo (17.1%) for PPF. In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).
特发性肺纤维化（IPF）和进行性肺纤维化（PPF）的发病率和死亡率都很高；因此，需要新的治疗方法。评估口服溶血磷脂酸受体1拮抗剂阿地帕兰特（BMS-986278）对IPF和PPF患者的疗效和安全性。这项2期随机双盲安慰剂对照试验纳入了IPF患者（随机分组278例，接受治疗276例）或PPF患者（随机分组125例，接受治疗123例）的平行队列，他们接受30毫克阿地帕兰特、60毫克阿地帕兰特或安慰剂（1:1:1），每日两次，共26周。允许使用背景抗纤维化药物（两个队列）和免疫抑制剂（仅PPF队列）。IPF患者在26周内预测FVC百分比的变化率分别为-2.7%（安慰剂）、-2.8%（30毫克）和-1.2%（60毫克），PPF患者分别为-4.3%（安慰剂）、-2.9%（30毫克）和-1.1%（60毫克）。60毫克阿地帕兰特与安慰剂之间的治疗差异，IPF为1.4%（95%置信区间，-0.1至3.0），PPF为3.2%（95%置信区间, 0.7至5.7）。在两个队列中，无论是否使用背景抗纤维化药物都观察到了治疗效果。阿地帕兰特组与安慰剂组腹泻发生率相似。在两个队列的所有组中均观察到给药后第1天血压短暂下降，但阿地帕兰特组下降幅度更大。因不良事件导致的治疗中断在IPF各治疗组中相似，在PPF中，阿地帕兰特组（2.5% [30毫克]；0% [60毫克]）低于安慰剂组（17.1%）。在这项评估IPF和PPF平行队列抗纤维化治疗的首次2期研究中，60毫克阿地帕兰特可减缓肺功能下降，且安全耐受性良好，支持在3期试验中进一步评估。临床试验已在clinicaltrials.gov注册，标识符为（NCT04308681）。
