在成年人患有支气管切除症时抑制Cathepsin C (dipeptidyl peptidase1):AIRLEAF,一个II期随机,双盲,安慰剂控制,剂量确定研究
James D Chalmers1, Michal Shteinberg2,3, Marcus A Mall4,5,6
1Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK j.chalmers@dundee.ac.uk.
这项研究表明,BI 1291583,一种新型的甲素C抑制剂,减少了成年人患有支气管切除症的恶化. 该药物表现出剂量依赖的益处,具有与安慰剂相似的有利安全概况.
科学领域:
- 肺部病理学 肺部病理学
- 药理学 药理学是指药理学的学科.
- 临床试验 临床试验
背景情况:
- 支气管切除症涉及无控制的中性粒细胞血清蛋白酶 (NSP) 活动.
- 甲素C (CatC) 在中性粒细胞成熟过程中激活NSP.
- CatC 抑制剂可能会减少中性粒细胞介导的肺损伤.
研究的目的:
- 评估一种新的CatC抑制剂BI 1291583的疗效,安全性和最佳剂量.
- 评估BI 1291583对成年人支气管切除症肺部恶化的影响.
- 确定BI 1291583的剂量反应关系.
主要方法:
- 第二阶段,随机,双盲,安慰剂对照试验 (AIRLEAF).
- 322名参与者接受了口服BI 1291583 (1mg,2.5mg,5mg) 或安慰剂24-48周.
- 剂量反应曲线分析使用时间到第一个肺部恶化;二级终点包括恶化的频率,肺功能和生活质量.
主要成果:
- 确立了BI 1291583的显著剂量依赖益处,即第一个恶化的时间 (调整后p=0.0448).
- BI 1291583 2.5mg和5mg数值降低了恶化的风险与安慰剂相比 (HRs 0.66和0.71).
- 2.5mg剂量显示出数量上优越的疗效; 1mg与安慰剂相似. 安全性概况与安慰剂可比.
结论:
- 治疗BI 1291583可降低成年人支气管切除症恶化的风险.
- 观察到剂量依赖的效果,2.5mg剂量显示出有希望的结果.
- BI 1291583提出了一个潜在的新疗法选择,用于管理支气管切除症.
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