BACKGROUND In the phase 3 SOLSTICE study (NCT02931539), maribavir was superior to investigator-assigned therapy (IAT) for confirmed cytomegalovirus viremia clearance at study week 8 in hematopoietic cell/solid organ transplant (HCT/SOT) recipients. We report additional efficacy and safety analyses from the SOT subgroup. METHODS Eligible solid organ transplant recipients (n=211) received maribavir 400 mg twice daily (n=142) or IAT (n=69) for 8 weeks (12 weeks' follow-up). Cytomegalovirus viremia clearance at week 8 (primary endpoint) and cytomegalovirus viremia clearance plus symptom control at the end of week 8 maintained through week 16 (key secondary endpoint) were assessed. Graft outcomes and treatment-emergent adverse events were analyzed. RESULTS A higher proportion maribavir-treated patients achieved the primary endpoint than with IAT across transplant organ types, including kidney (maribavir: 59.5%, IAT: 34.4%), lung (47.5%, 13.6%), and heart (42.9%, 11.1%). Similar proportions of patients achieved the key secondary endpoint in both arms (13.4% versus 11.6%; adjusted difference: 2.4%; 95% CI: -7.05, 11.83%; p=0.620). Rates of treatment-emergent adverse events were: maribavir (96.5%), IAT (88.4%). Maribavir (3.5%) had fewer treatment discontinuations due to treatment-emergent adverse events than IAT (23.2%). There were no graft losses; patients in both arms experienced acute rejection (maribavir: 9 [6.3%]; IAT: 4 [5.8%]). Treatment-emergent maribavir mutations occurred in 28.2% of patients; 19/33 patients achieved viremia clearance with subsequent alternative treatment. CONCLUSIONS Consistent with findings in the overall SOLSTICE population, this subgroup analysis of SOT recipients demonstrated greater effectiveness of maribavir for cytomegalovirus viremia clearance and fewer discontinuations due to treatment-emergent adverse events than IAT. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov; NCT02931539 DATA AVAILABILITY STATEMENT: The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants data supporting the results reported in this article, will be made available within three months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after its deidentification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization.

中文翻译：

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Maribavir 治疗实体器官移植受者的难治性巨细胞病毒感染（有或没有耐药性）：3 期随机 SOLSTICE 研究的亚组分析。


背景 在 3 期 SOLSTICE 研究 （NCT02931539） 中，maribavir 在研究第 8 周确认造血细胞/实体器官移植 （HCT/SOT） 受者巨细胞病毒病毒血症清除方面优于研究者分配的疗法 （IAT）。我们报告了 SOT 亚组的其他疗效和安全性分析。方法 符合条件的实体器官移植受者 （n=211） 接受 maribavir 400 mg，每天两次 （n=142） 或 IAT （n=69），持续 8 周 （12 周随访）。评估了第 8 周的巨细胞病毒病毒血症清除率（主要终点）和第 8 周结束时的巨细胞病毒病毒血症清除率加上症状控制，并维持到第 16 周（关键次要终点）。分析移植物结局和治疗中出现的不良事件。结果在移植器官类型中，马里巴韦治疗患者达到主要终点的比例高于 IAT，包括肾脏 （maribavir： 59.5%， IAT： 34.4%）、肺 （47.5%， 13.6%） 和心脏 （42.9%， 11.1%）。两组达到关键次要终点的患者比例相似（13.4% vs 11.6%;调整后差异：2.4%;95% CI：-7.05,11.83%;p=0.620）。治疗中出现的不良事件发生率为：maribavir （96.5%）、IAT （88.4%）。Maribavir （3.5%） 因治疗中出现的不良事件而停止治疗的次数少于 IAT （23.2%）。没有移植物损失;两组患者均出现急性排斥反应 （maribavir： 9 [6.3%];IAT：4 [5.8%]）。治疗中出现的 maribavir 突变发生在 28.2% 的患者中;19/33 例患者在随后的替代治疗中实现了病毒血症清除。 结论 与整个 SOLSTICE 人群的结果一致，SOT 接受者的亚组分析表明，与 IAT 相比，maribavir 对巨细胞病毒病毒血症清除的有效性更高，并且因治疗中出现的不良事件而停药的次数更少。临床试验注册号 ClinicalTrials.gov;NCT02931539 数据可用性声明：数据集，包括经过编辑的研究方案、经过编辑的统计分析计划以及支持本文报告结果的个人参与者数据，将在最初请求后的三个月内提供给提供方法学合理建议的研究人员。数据将在去标识化后提供，以遵守适用的隐私法、数据保护以及同意和匿名化的要求。