RATIONALE Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. OBJECTIVES Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. METHODS This phase 2, randomized, double-blind, placebo-controlled trial 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 admilparant, 60-mg admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted. MEASUREMENTS AND MAIN RESULTS Rates of change in percentage of predicted forced vital capacity (ppFVC) 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% CI, -0.1 to 3.0) for IPF and 3.2% (95% CI, 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 post-dose blood pressure reductions were observed in all arms in both cohorts but greater with admilparant. Treatment discontinuations due to adverse events were similar across IPF arms and lower with admilparant (2.5% [30-mg]; 0% [60-mg]) versus placebo (17.1%) for 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. Clinical trial registration available at www. CLINICALTRIALS gov, ID: NCT04308681.

中文翻译：

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LPA1 拮抗剂 Admilparant 治疗肺纤维化的疗效和安全性：一项 2 期随机临床试验。


基本原理特发性肺纤维化 （IPF） 和进行性肺纤维化 （PPF） 的发病率和死亡率很高;因此，需要新的治疗方法。目的 评估口服溶血磷脂酸受体 1 受体拮抗剂 admilparant （BMS-986278） 在 IPF 和 PPF 患者中的疗效和安全性。方法 这项 2 期、随机、双盲、安慰剂对照试验包括 IPF （n = 278 随机分配，n = 276 治疗） 或 PPF （n = 125 随机分配，n = 123 治疗）患者的平行队列，他们接受 30 mg admilparant、60 mg admilparant 或安慰剂 （1：1：1） 每天两次，持续 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）。测量和主要结果IPF 在 26 周内预测用力肺活量 （ppFVC） 百分比的变化率为 -2.7%（安慰剂）、-2.8%（30 毫克）和 -1.2%（60 毫克），PPF 为 -4.3%（安慰剂）、-2.9%（30 毫克）和 -1.1%（60 毫克）。60 mg 阿米帕特和安慰剂之间的治疗差异为 IPF 为 1.4% （95% CI，-0.1 至 3.0），PPF 为 3.2% （95% CI，0.7 至 5.7）。在两个队列中观察到有或没有背景抗纤维化治疗的治疗效果。与安慰剂组相比，阳性组腹泻的发生频率相似。在两个队列的所有组中，所有组均观察到给药后第 1 天的短暂血压降低，但 admilparant 的血压降低幅度更大。IPF 组因不良事件而停止治疗的情况相似，而 PPF 组与安慰剂 （17.1%） 相比，阿米帕尔 （2.5% [30-mg];0% [60-mg]） 的治疗中断率较低。结论 在第一项 2 期研究中，在平行 IPF 和 PPF 队列中评估抗纤维化治疗，60 mg admilparant 减缓了肺功能下降，并且安全且耐受性良好，支持 3 期试验的进一步评估。 临床试验注册可在 www.CLINICALTRIALS gov，ID：NCT04308681。