Effect of Admilparant, a Lysophosphatidic Acid Receptor 1 Antagonist, on Disease Progression in Pulmonary Fibrosis.

Admilparant (BMS-986278) is an oral lysophosphatidic acid receptor 1 antagonist under development for treatment of IPF and PPF.

Admilparant（BMS-986278）是一种正在开发中用于治疗IPF和PPF的口服溶血磷脂酸受体1拮抗剂。

research_question

How does admilparant affect time to disease progression in patients with IPF or PPF?

Admilparant 如何影响特发性肺纤维化（IPF）或肺泡蛋白沉着症（PPF）患者的疾病进展时间？

study_design_and_methods

In a phase 2, randomized, double-anonymized, placebo-controlledstudy, parallel cohorts of patients with IPF or PPF were randomized separately 1:1:1 to receive 30 mg admilparant, 60 mg admilparant, or placebo twice daily for 26 weeks; background antifibrotics were allowed.

在这项 II 期、随机、双盲、安慰剂对照研究中，分别将特发性肺纤维化（IPF）或肺泡蛋白沉着症（PPF）患者随机分为 1:1:1 的平行队列，分别接受每日两次 30 mg 或 60 mg 的 Admilparant 或安慰剂治疗 26 周；允许使用背景抗纤维化药物。

The effect of admilparant vs placebo on time to disease progression was assessed post hoc.

对接受药物与安慰剂对疾病进展时间的影响进行了事后评估。

Disease progression was defined as a composite of relative decline of ≥ 10% in percent predicted FVC (ppFVC), acute exacerbation, all-cause hospitalization, and all-cause mortality.

疾病进展被定义为相对预测用力肺活量（ppFVC）下降≥10%，急性加重，全因住院和全因死亡的复合结果。

Subgroup analyses were performed based on median ppFVC at baseline.

基于基线中位数ppFVC进行了亚组分析。

A Kaplan-Meier product-limit approach assessed time to first event of disease progression over 26 weeks.

采用Kaplan-Meier乘限法评估了26周内疾病进展首次事件的时间。

Results

In total, 255 patients with IPF and 114 patients with PPF were included.

总共纳入了255名特发性肺纤维化(IPF)患者和114名肺泡蛋白质沉积症(PPF)患者。

Median ppFVC at baseline was 77.3% and 64.7% in the IPF and PPF cohorts, respectively.

基线时，IPF队列和PPF队列的中位数ppFVC分别为77.3%和64.7%。

Treatment with 60 mg admilparant delayed time to disease progression over 26 weeks compared with placebo in both cohorts of patients (IPF: hazard ratio, 0.54; 95% CI, 0.31-0.95; PPF: hazard ratio, 0.41; 95% CI, 0.18-0.90).

使用60 mg的admilparant治疗超过26周，与安慰剂相比，延缓了两组患者的疾病进展时间（IPF：风险比，0.54；95%置信区间，0.31-0.95；PPF：风险比，0.41；95%置信区间，0.18-0.90）。

A similar trend was observed in the subgroup analysis of patients with ppFVC at baseline either below or above the median value.

在基线时ppFVC低于或高于中位数的患者亚组分析中，观察到类似的趋势。

In both cohorts, the most frequent first event was relative decline of ≥ 10% in ppFVC; no deaths were reported as first progression events.

在这两个队列中，最常见的首次事件是ppFVC相对下降≥10%；没有首次进展事件报告为死亡。

interpretation

These findings support further evaluation of admilparant as a therapeutic option for patients with IPF or PPF in phase 3 trials.

这些发现支持进一步评估admilparant作为IPF或PPF患者治疗选择，在III期试验中的潜力。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT04308681; URL: www.

ClinicalTrials.gov; 编号: NCT04308681; 网址: www.

clinicaltrials

gov.

5年总生存率为65%，95%置信区间为58-72%。