一个用于治疗WHIM综合征的CXCR4抗剂mavorixafor的3期随机试验
Raffaele Badolato1, Laia Alsina2,3,4, Antoine Azar5
1Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili, Brescia, Italy.
Blood
|April 21, 2024
概括
在WHIM综合征患者中,Mavorixafor显著改善了中性粒细胞和淋巴细胞的数量,导致感染较少和不那么严重. 这种CXCR4抗剂在第三阶段试验中表现出良好的安全性.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- ,低型球蛋白血症,感染和骨髓灰质炎综合征 (WHIM) 是一种罕见的原发性免疫缺陷.
- 它是由CXCR4基因的功能增益变异引起的,导致免疫细胞贩运受损.
研究的目的:
- 评估口服CXCR4抗剂马沃里克萨福的疗效和安全性,用于WHIM综合征患者.
- 评估mavorixafor对免疫细胞数量和感染率的影响.
主要方法:
- 这是一项随机,双盲,安慰剂控制的3期试验,涉及31名患有WHIM综合征的参与者 (≥12年).
- 参与者每天接受马沃里克萨福或安慰剂,持续52周.
- 主要终点:超出绝对中性细胞计数值 (TATANC) 的时间;次要终点包括超出绝对淋巴细胞计数值 (TATALC) 的时间和感染率.
主要成果:
- 与安慰剂相比,Mavorixafor显著增加了TATANC (15.0与2.8小时) 和TATALC (15.8与4.6小时) (P <.001).与安慰剂相比,Mavorixafor显著增加了TATANC (15.0与2.8小时) 和TATALC (15.8与4.6小时).
- 马沃里克萨福的年化感染率降低了60% (1.7比4.2),总感染得分降低了40%.
- 减少感染频率,严重程度,持续时间和抗生素使用,没有与治疗相关的严重不良事件.
结论:
- 马沃里克萨福在改善免疫细胞数量和减少WHIM综合征感染负担方面表现出显著的疗效.
- 药物耐受性很好,这表明在治疗这种罕见的免疫缺陷时,药物具有良好的安全性.
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