Ljungman Per, Bermudez Arancha, Logan Aaron C, Kharfan-Dabaja Mohamed A, Chevallier Patrice, Martino Rodrigo, Wulf Gerald, Selleslag Dominik, Kakihana Kazuhiko, Langston Amelia, Lee Dong-Gun, Solano Carlos, Okamoto Shinichiro, Smith Larry R, Boeckh Michael, Wingard John R, Cywin Beth, Fredericks Christine, Lademacher Christopher, Wang Xuegong, Young James, Maertens Johan
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, SE-14186, Stockholm, Sweden.
Department of Hematology, Hospital Universitario Marqués de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla, 39008, Santander, Spain.
EClinicalMedicine. 2021 Mar 19;33:100787. doi: 10.1016/j.eclinm.2021.100787. eCollection 2021 Mar.
Cytomegalovirus (CMV) is a complication of allogeneic haematopoietic cell transplantation (allo-HCT). ASP0113, a DNA-based vaccine, contains two plasmids encoding human CMV glycoprotein B and phosphoprotein 65 (pp65). We assessed ASP0113 in CMV-seropositive allo-HCT recipients.
In this phase 3, randomised, placebo-controlled study, CMV-seropositive allo-HCT recipients were randomly assigned (1:1) via interactive response technology to receive five injections of 1 mL of 5 mg/mL ASP0113 or placebo. The pharmacist and designated staff were unblinded. Masked syringes maintained the blind for patients and study personnel. Efficacy and safety analyses included patients who received ≥1 dose of ASP0113/placebo. The primary efficacy endpoint was the proportion of allo-HCT recipients with composite all-cause mortality and adjudicated CMV end-organ disease (EOD) by 1 year post-transplant. ClinicalTrials.gov: NCT01877655 (not recruiting).
Patients were recruited between Sept 11, 2013 and Sept 21, 2016. Overall, 501 patients received ≥1 dose of ASP0113 ( = 246) or placebo ( = 255). The proportion of patients with composite all-cause mortality and adjudicated CMV EOD by 1 year post-transplant was 35.4% ( = 87) with ASP0113 and 30•2% ( = 77) with placebo (odds ratio 1.27; 95% confidence interval: 0.87 to 1.85; = 0.205). Incidence of injection site-related treatment-emergent adverse events (TEAEs) was higher with ASP0113 than placebo. Overall incidence and severity of other TEAEs was similar between groups. T-cell response to pp65 increased over time and was greater with placebo than ASP0113 ( = 0.027).
ASP0113 did not reduce overall mortality or CMV EOD by 1 year post-transplant. Safety findings were similar between groups.
Astellas Pharma Global Development, Inc .
巨细胞病毒（CMV）是异基因造血细胞移植（allo-HCT）的一种并发症。ASP0113是一种基于DNA的疫苗，包含两种编码人CMV糖蛋白B和磷蛋白65（pp65）的质粒。我们在CMV血清学阳性的allo-HCT受者中评估了ASP0113。
在这项3期随机安慰剂对照研究中，CMV血清学阳性的allo-HCT受者通过交互式应答技术被随机分配（1:1）接受5次1 mL 5 mg/mL ASP0113或安慰剂注射。药剂师和指定工作人员未设盲。带面罩的注射器对患者和研究人员保持盲态。疗效和安全性分析纳入接受≥1剂ASP0113/安慰剂的患者。主要疗效终点是移植后1年内发生全因死亡和经判定的CMV终末器官疾病（EOD）的allo-HCT受者比例。ClinicalTrials.gov：NCT01877655（未招募）。
患者于2013年9月11日至2016年9月21日入组。总体而言，501例患者接受了≥1剂ASP0113（n = 246）或安慰剂（n = 255）。移植后1年时，发生全因死亡和经判定的CMV EOD的患者比例，接受ASP0113的为35.4%（n = 87），接受安慰剂的为30.2%（n = 77）（比值比1.27；95%置信区间：0.87至1.85；P = 0.205）。ASP0113注射部位相关治疗中出现的不良事件（TEAE）发生率高于安慰剂。其他TEAE的总体发生率和严重程度在两组之间相似。对pp65的T细胞反应随时间增加，安慰剂组比ASP0113组更强（P = 0.027）。
ASP0113在移植后1年时未降低总体死亡率或CMV EOD。两组的安全性结果相似。
安斯泰来制药全球开发公司。
