Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study
Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study
复制标题
DOI：
10.1111/tri.12225
复制
发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Budde, Klemens
中科院分区：
文献类型：
--
作者：
Stoelben, Susanne;Arns, Wolfgang;Budde, Klemens
巨细胞病毒(CMV)感染仍然是移植受者发病率和死亡率的重要原因。来特莫韦(AIC246)是一种正在开发中的抗巨细胞病毒新药，通过新的作用机制发挥作用。在这项首次给患者服用来特莫韦的概念验证试验中，27名CMV复制活跃的移植受者被随机分配到为期14天的口服治疗方案中，每天两次，每次40毫克，每天一次，或者在一项多中心开放标签试验中接受当地标准护理(SOC)。评估了有效性、安全性和有限的药代动力学参数。所有治疗组的巨细胞病毒DNA拷贝数较治疗前均有统计学意义的下降(40mgBID：P=0.031；80mgQD：P=0.018；SOC：P=0.001)，而治疗组之间的病毒载量降低比较，差异无统计学意义。LETERMOVER组12名患者中有6名(50%)病毒清除，而7名SOC患者中有2名(28.6%)。LETERMOVR治疗总体耐受性良好，在试验期间没有患者出现CMV病。两种利特莫韦治疗方案都导致了同样高的谷值血浆浓度。在这些病毒移植受者身上观察到的有效性、安全性和药代动力学表明，来特莫夫是一种很有前途的抗CMV新药。
Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in transplant recipients. Letermovir (AIC246), is a novel anti-HCMV drug in development, acting via a novel mechanism of action. In this proof-of-concept trial with first administration of letermovir to patients, 27 transplant recipients with active CMV replication were randomly assigned to a 14-day oral treatment regimen of either letermovir 40mg twice a day, letermovir 80mg once a day, or local standard of care (SOC) in a multicenter, open-label trial. Efficacy, safety, and limited pharmacokinetic parameters were assessed. All groups had a statistically significant decrease in CMV-DNA copy number from baseline (40mgBID: P=0.031; 80mg QD: P=0.018; SOC:P=0.001), and comparison of viral load reduction between treatment groups showed no statistically significant differences. Viral clearance was achieved for 6 of 12 patients (50%) in the letermovir groups versus two of seven SOC patients (28.6%). Letermovir treatment was generally well tolerated, no patient developed CMV disease during the trial. Both letermovir treatment regimens resulted in equally high trough level plasma concentrations. The efficacy, safety, and pharmacokinetics observed in these viremic transplant recipients indicate that letermovir is a promising new anti-CMV drug.