3随机试验阶段Voxelotor镰状细胞病。

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Vichinsky E,霍普CC、Ataga KI、再保险、Nduba V, El-Beshlawy, Hassab H,阿奇比MM, Alkindi年代,布朗RC Diuguid DL,电动高架索道P, Tsitsikas哒,Elghandour, Gordeuk VR,坎特J先生说道,Lehrer-Graiwer J, Tonda M, Intondi,通B,霍华德·J

3随机试验阶段Voxelotor镰状细胞病。

郑传经地中海J。2019年8月8日,381 (6):509 - 519。doi: 10.1056 / NEJMoa1903212。Epub 2019年6月14日。

PubMed ID

31199090 (在PubMed

]

文摘

背景:缺氧镰状血红蛋白(HbS)聚合驱动器镰状细胞病的病理生理学。因此,哈佛商学院的直接抑制聚合有潜力良好修改疾病的结果。Voxelotor是哈佛商学院的阻聚剂。方法:多中心,第三阶段,双盲、随机、安慰剂对照试验,我们比较两个剂量的疗效和安全性级别的voxelotor(1500毫克和900毫克,每日口服一次)与安慰剂与镰状细胞病的人。主要终点是参与者的比例血红蛋白反应,被定义为增加超过1.0克每分升的基线在24周意向处理分析。结果:共有274名参与者被随机分配比例比接受每日一剂口服1500毫克的voxelotor, voxelotor 900毫克或安慰剂。大多数参与者有镰状细胞性贫血(纯合血红蛋白S或血红蛋白Sbeta(0)地中海贫血),和大约三分之二接受羟基脲在基线。在意向处理分析中,参与者的比例明显高于1500毫克的血红蛋白反应voxelotor组(51%;95%可信区间(CI), 41 - 61)比安慰剂组(7%;95%可信区间,1 - 12)。 Anemia worsened between baseline and week 24 in fewer participants in each voxelotor dose group than in those receiving placebo. At week 24, the 1500-mg voxelotor group had significantly greater reductions from baseline in the indirect bilirubin level and percentage of reticulocytes than the placebo group. The percentage of participants with an adverse event that occurred or worsened during the treatment period was similar across the trial groups. Adverse events of at least grade 3 occurred in 26% of the participants in the 1500-mg voxelotor group, 23% in the 900-mg voxelotor group, and 26% in the placebo group. Most adverse events were not related to the trial drug or placebo, as determined by the investigators. CONCLUSIONS: In this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis. These findings are consistent with inhibition of HbS polymerization and indicate a disease-modifying potential. (Funded by Global Blood Therapeutics; HOPE ClinicalTrials.gov number, NCT03036813.).

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Voxelotor