Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Objectives: Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. Methods: This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in fibrosis-related biomarkers. Measurements and Main Results: Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Participants who were treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those who received placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging, and a decrease in fibrosis-associated biomarkers was observed with bexotegrast versus placebo. Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registered with www.clinicaltrials.gov (NCT04396756).

中文翻译：

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贝索格斯特治疗特发性肺纤维化患者：INTEGRIS-IPF 临床试验。


理由：特发性肺纤维化 (IPF) 是一种罕见的进行性疾病，可导致进行性咳嗽、劳力性呼吸困难、生活质量受损和死亡。目的：Bexotegrast (PLN-74809) 是一种口服、每日一次的研究药物，正在开发用于治疗 IPF。方法：这项 2a 期多中心临床试验随机分配患有 IPF 的参与者，每天一次口服贝索格斯特 40 mg、80 mg、160 mg 或 320 mg，或安慰剂，有或没有背景 IPF 治疗（吡非尼酮或尼达尼布） ），每个贝索格斯特剂量组的比例约为 3:1，持续至少 12 周。主要终点是治疗引起的不良事件（TEAE）的发生率。探索性疗效终点包括 FVC 相对于基线的变化、定量肺纤维化 (QLF) 程度 (%) 以及纤维化相关生物标志物相对于基线的变化。测量和主要结果：贝索司特耐受性良好，合并贝索司特组和安慰剂组的 TEAE 发生率相似（分别为 62/89 [69.7%] 和 21/31 [67.7%]）。腹泻是最常见的 TEAE；大多数患有腹泻的参与者也接受了尼达尼布治疗。与接受安慰剂的受试者相比，接受贝索格司特治疗的受试者在 12 周内的 FVC 下降有所减少，无论有或没有背景治疗。通过 QLF 成像观察到贝索格斯特的剂量依赖性抗纤维化作用，并且与安慰剂相比，贝索格斯特观察到纤维化相关生物标志物的减少。结论：Bexotegrast 表现出良好的安全性和耐受性，所研究的剂量长达 12 周。根据 FVC、QLF 成像和纤维化生物标志物的循环水平，探索性分析表明具有抗纤维化作用。临床试验已在 www.www. 注册。临床试验.gov (NCT04396756)。