性结肠炎的临床试验设计:根据韦多利祖马布第三阶段试验GEMINI 1和VISIBLE 1的后期分析解释不断变化的终点
William J Sandborn1, Bruce E Sands2, Sharif Uddin3
1Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
梅奥总得分,包括医生全球评估 (PGA),历来用于性结肠炎 (UC) 试验. 修改后的梅奥得分,不包括PGA,符合FDA的指导方针,并且在UC临床试验中显示出对vedolizumab的可比疗效.
科学领域:
- 胃肠病学 胃肠病学
- 临床试验设计 临床试验设计
- 药物经济学 药物经济学
背景情况:
- 梅奥总得分为12分,包括医生的全球评估 (PGA),一直是评估性结肠炎 (UC) 临床试验结果的标准.
- 2016年,美国FDA的指导建议将PGA从未来的UC试验终点中删除.
- 本研究研究了UC试验终点的演变,并将9点修改后的梅奥得分 (不包括PGA) 与总梅奥得分进行比较.
研究的目的:
- 在性结肠炎 (UC) 第三阶段试验中分析临床缓解终点定义的演变.
- 在GEMINI 1和VISIBLE 1试验的后期分析中,使用修改的梅奥得分与总梅奥得分来比较vedolizumab的疗效.
主要方法:
- 从已发表的文献和ClinicalTrials.gov中提取了UC第3期试验的临床缓解的终点定义.
- 进行了GEMINI 1和VISIBLE 1试验的后期分析,测量了使用四个定义对vedolizumab和安慰剂的52周临床缓解率 (%Δ) 的差异.
- 从修改后的梅奥得分得出的%Δ值与总梅奥得分得出的值进行比较.
主要成果:
- 在2020年之前完成的试验主要使用梅奥总得分,而后来的试验采用了修改后的梅奥得分.
- 后期分析表明,降低终点严格度与增加的% Δ值相关.
- 修改后的梅奥得分定义与FDA建议最接近,产生了与GEMINI 1和VISIBLE 1中梅奥总得分得到的值相似的%Δ值.
结论:
- 根据FDA的建议,UC临床试验终点定义已经发展.
- 维多利祖马布在UC的疗效,当使用修改的梅奥得分进行评估时,显示了与使用传统的梅奥总得分报告的结果相似的结果.
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