基洛菲克索在非肝硬化原发性硬化性脑膜炎 (PRIMIS):一个随机,双盲,多中心,安慰剂控制的,第三阶段试验
Michael Trauner1, Cynthia Levy2, Atsushi Tanaka3
1Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
The lancet. Gastroenterology & hepatology
|October 31, 2025
概括
基洛菲克索没有减缓原发性硬化胆道炎 (PSC) 纤维化进展. 更多的Cilofexor患者经历了,这突出了这一类药物的重要安全数据.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 胃肠病学 胃肠病学
- 临床药理学 临床药理学
背景情况:
- 初级硬化性胆道炎 (PSC) 目前缺乏经过验证的药理疗法来改变其自然过程.
- 华氏体X激活受体 (FXR) 激动剂基洛菲克索 (Cilofexor) 在非肝性PSC中被研究其疗效和安全性.
- 这项研究解决了在PSC管理中有效治疗的关键未满足需求.
研究的目的:
- 评估Cilofexor在减少非肝硬化PSC患者肝纤维化进展方面的疗效.
- 与安慰剂相比,评估 cilofexor 的安全性和耐受性.
- 提供关于FXR激应剂在PSC治疗中的潜力的数据.
主要方法:
- 一个第三阶段,双盲,安慰剂控制,多中心试验,涉及18-75岁的成年人,非肝硬化PSC (F0-F3).
- 参与者被随机分配 (2:1) 接受 cilofexor 100 mg 或安慰剂口服每天一次,持续96周.
- 主要终点是组织学性肝纤维化进展,并进行二次安全性评估.
主要成果:
- 该研究因徒劳而提前终止;与安慰剂相比,Cilofexor没有显著减少纤维化进展 (31%对33%,p=0.42).
- 在 cilofexor 组 (49%) 中, Pruritus 是比安慰剂 (36%) 更常见的不良事件,其中 4% 的 cilofexor 接受者有 3 级或更高的事件.
- 严重不良事件的比例在两组之间相似 (19%),并且没有发生与治疗相关的死亡.
结论:
- 基洛菲克索在减少非肝硬化PSC患者肝纤维化进展方面没有显著的益处.
- 在 cilofexor 组中的发病率增加为 FXR 激活剂提供了关键的安全信息.
- 这项试验为PSC研究中Cilofexor和相关化合物的有价值的危害数据做出了贡献.
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