Dual αvβ6 and αvβ1 Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial.

Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of αvβ6 and αvβ1 integrins under late-stage evaluation for treatment of IPF.

Bexotegrast (PLN-74809) 是一种口服、每日一次的αvβ6和αvβ1整合素双重选择性抑制剂，目前正处于晚期评估阶段，用于治疗IPF。

Objectives: To evaluate changes in type I collagen in the lungs of participants with IPF after treatment with bexotegrast.

目的：评估IPF患者在使用bexotegrast治疗后肺部I型胶原蛋白的变化。

Methods: In this phase 2 (NCT05621252), single-center, double-blind, placebo-controlledstudy, adults with IPF received bexotegrast 160 mg or placebo for 12 weeks.

方法：在这项II期（NCT05621252）、单中心、双盲、安慰剂对照研究中，患有IPF的成年人接受了160毫克的bexotegrast或安慰剂治疗，为期12周。

The primary endpoint was the change in whole-lung standardized uptake value of 68Ga-CBP8 positron emission tomography.

主要终点是68Ga-CBP8正电子发射断层扫描全肺标准化摄取值的变化。

Changes in lung dynamic contrast-enhanced magnetic resonance imaging parameters, FVC, cough severity, and biomarkers of collagen synthesis and progressive disease were also assessed.

还评估了肺部动态对比增强磁共振成像参数、用力肺活量(FVC)、咳嗽严重程度以及胶原合成和疾病进展的生物标志物的变化。

Measurements and Main Results: Of 10 participants, 7 received bexotegrast and 3 received placebo.

测量和主要结果：在10名参与者中，7人接受了贝索替格拉斯特治疗，3人接受了安慰剂。

At Week 12, the mean change from baseline in the top quartile of 68Ga-CBP8 whole-lung standardized uptake value was -1.2% with bexotegrast versus 6.6% with placebo; the greatest mean changes were observed in subpleural lung regions in both groups (bexotegrast, -3.7%; placebo, 10.3%).

在第12周时，68Ga-CBP8全肺标准化摄取值最高四分位数的基线平均变化为贝索替格拉斯特组为-1.2%，而安慰剂组为6.6%；在两组中观察到最大的平均变化均出现在肺外周区域（贝索替格拉斯特组为-3.7%，安慰剂组为10.3%）。

Dynamic contrast-enhanced magnetic resonance imaging showed numerically increased peak enhancement and faster contrast washout rate in bexotegrast-treated participants, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume.

动态对比增强磁共振成像显示接受贝索替格拉斯特治疗的参与者在峰值增强方面数值上有所增加，对比剂清除速率更快，这表明肺部微血管有所改善，血管外细胞外体积减少。

Bexotegrast treatment resulted in numerical improvements in FVC, cough severity, and biomarkers.

贝索替格拉斯特治疗在数值上改善了用力肺活量（FVC）、咳嗽严重程度和生物标志物。

Conclusions: The reduced uptake of 68Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling.

结论：参与者的肺部对68Ga-CBP8的摄取减少表明了bexotegrast具有抗纤维化作用，这表明了肺部良好重塑的潜力。

Clinical trial registered with www.clinicaltrials.gov (NCT05621252).

临床试验已在www.clinicaltrials.gov注册（NCT05621252）。