关于 voxelotor 治疗镰状细胞病腿部溃疡的 3 期、随机、安慰剂对照试验：RESOLVE。
完整摘要 · 中文译文
腿部溃疡是镰状细胞病（SCD，包括镰状细胞贫血及其他镰状细胞病）的一种致衰性并发症，且尚无经证实有效的治疗方法。Voxelotor治疗镰状细胞病腿部溃疡愈合（RESOLVE）是一项3期、随机、双盲、安慰剂对照试验，评估voxelotor对年龄≥12岁、患有SCD（纯合血红蛋白S [HbSS]/血红蛋白S β0-地中海贫血 [HbSβ0]）且至少有1处活动性下肢皮肤溃疡的受试者腿部溃疡愈合的作用。来自肯尼亚、尼日利亚和巴西的受试者按1:1随机分配接受voxelotor 1500 mg（N = 45）或安慰剂（N = 43）治疗12周。主要终点为第12周时所有目标溃疡完全愈合，未达到（愈合率：voxelotor组6.7% [3/45]，安慰剂组7.0% [3/43]；双侧p > 0.99）。第12周后，两组均接受开放标签的voxelotor治疗。在此期间，由于包括RESOLVE在内的四项voxelotor试验的初步数据显示出需要进一步分析的安全信号和潜在风险，2024年5月暂停给药。2024年9月，voxelotor从全球所有市场撤出，该试验随之终止。在RESOLVE的最终安全性分析中，最常见的与SCD相关的治疗中出现的不良事件（TEAE）为镰状细胞贫血伴危象（随机期：voxelotor组44.4%，安慰剂组25.6%；开放标签期：继续使用voxelotor组60.5%，延迟使用voxelotor组53.5%）。11名受试者发生致死性事件，其中9名在接受voxelotor期间，2名在voxelotor暂停后（1名约1周后；1名约4个月后）；没有死亡被认为与治疗相关。 ment相关。总之，腿部溃疡的消退在各组之间相似，沃塞洛托组的治疗中出现的不良事件（TEAEs）发生率较高。
完整摘要 · 英文原文
Leg ulcers are a debilitating complication of sickle cell disease (SCD, including sickle cell anaemia and other sickle cell disorders) and have no proven treatments. Resolution of Sickle Cell Leg Ulcers with Voxelotor (RESOLVE) was a Phase 3, randomised, double-blind, placebo-controlled trial evaluating voxelotor for leg ulcer resolution in participants aged ≥12 years with SCD (homozygous haemoglobin S [HbSS]/haemoglobin S β0-thalassaemia [HbSβ0]) and ≥1 active cutaneous lower-extremity ulcer. Participants from Kenya, Nigeria and Brazil were randomised 1:1 to voxelotor 1500 mg (N = 45) or placebo (N = 43) for 12 weeks. The primary end-point, complete resolution of all target ulcer(s) at Week 12, was not met (achieved resolution: voxelotor 6.7% [3/45], placebo 7.0% [3/43]; two-sided p > 0.99). After Week 12, both groups received open-label voxelotor. During this period, dosing was paused in May 2024, when preliminary data from four voxelotor trials, including RESOLVE, showed safety signals and potential risks that required further analysis. The trial was discontinued in September 2024 when voxelotor was withdrawn from all markets globally. In final safety analyses for RESOLVE, the most common SCD-related treatment-emergent adverse event (TEAE) was sickle cell anaemia with crisis (randomised period: voxelotor 44.4%, placebo 25.6%; open-label period: continuing-voxelotor 60.5%, delayed-voxelotor 53.5%). Eleven participants had fatal events, nine when receiving voxelotor and two after voxelotor was paused (one after ~1 week; one after ~4 months); no deaths were considered treatment-related. In conclusion, leg ulcer resolution was similar between groups, and the voxelotor arm had a higher rate of TEAEs.