Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial.

Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF.

目标：评估口服溶血磷脂酸受体1拮抗剂admilparant（BMS-986278）在IPF和PPF患者中的疗效和安全性。

Methods: This phase 2, randomized, double-blind, placebo-controlledtrial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks.

方法：这项2期、随机、双盲、安慰剂对照试验包括了并行队列的特发性肺纤维化（IPF）患者（随机人数为278，治疗人数为276）和慢性纤维化性间质性肺炎（PPF）患者（随机人数为125，治疗人数为123），他们分别接受了30毫克或60毫克的admilparant，或安慰剂（比例为1:1:1），每日两次，持续26周。

Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted.

背景：允许使用抗纤维化药物（两个队列均可）和免疫抑制剂（仅PPF队列）。

Measurements and Main Results: 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).

测量和主要结果：在26周内，IPF患者的预测FVC百分比变化率为-2.7%（安慰剂组）、-2.8%（30毫克组）和-1.2%（60毫克组），PPF患者的变化率为-4.3%（安慰剂组）、-2.9%（30毫克组）和-1.1%（60毫克组）。

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.

60毫克药物与安慰剂治疗差异为IPF患者1.4%（95%置信区间，-0.1至3.0）和PPF患者3.2%（95%置信区间，0.7至5.7）。

Treatment effect was observed with or without background antifibrotics in both cohorts.

无论是否使用背景抗纤维化药物，在两个队列中都观察到了治疗效果。

Diarrhea occurred at similar frequencies in admilparant arms versus placebo.

在试验药物组与安慰剂组中，腹泻的发生频率相似。

Transient Day 1 postdose blood pressure reductions were observed in all arms in both cohorts but were greater with admilparant.

在两个队列的所有组中，观察到用药后第1天血压短暂下降，但与admilparant组相比更大。

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.

因不良事件导致的治疗中断在IPF组中相似，并且与安慰剂（17.1%）相比，admilparant组较低（30 mg为2.5%；60 mg为0%）对于PPF。

Conclusions: 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.

结论：在首个评估抗纤维化治疗的2期研究中，同时对特发性肺纤维化（IPF）和肺泡蛋白沉积症（PPF）队列进行了平行研究，60毫克的admilparant减缓了肺功能下降，并且安全且耐受性良好，支持在3期试验中进一步评估。

Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).

该临床试验已在clinicaltrials.gov注册，注册号为（NCT04308681）。