Mori Takehiko, Kanda Yoshinobu, Takenaka Katsuto, Okamoto Shinichiro, Kato Jun, Kanda Junya, Yoshimoto Goichi, Gondo Hisashi, Doi Sayaka, Inaba Masaki, Kodera Yoshihisa
Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.
Int J Hematol. 2017 Feb;105(2):206-212. doi: 10.1007/s12185-016-2110-3. Epub 2016 Oct 28.
Cytomegalovirus (CMV) infection/reactivation is a serious complication after hematopoietic cell transplantation (HCT). The DNA vaccine ASP0113 contains two plasmids encoding CMV antigens (glycoprotein B and tegument phosphoprotein 65) that stimulate humoral and cellular immunity. Between June 2013 and February 2014, Astellas conducted a phase 2, open-label, uncontrolled, three-center trial to investigate the safety and tolerability of ASP0113 in Japanese patients undergoing HCT for hematologic disorders. Ten patients aged 22-61 years were enrolled; nine received at least one dose of ASP0113. Six patients received all five doses of ASP0113 5 mg at intervals before and after HCT. Pre-emptive antiviral therapy was allowed. One patient died following relapse of primary disease. All patients had serious adverse events deemed unrelated to ASP0113. CMV viremia (assessed by CMV antigenemia) occurred in seven patients, who then received anti-CMV therapy. No patients developed CMV end-organ disease. Adverse events associated with ASP0113 injection included pyrexia (three patients), skin reactions [injection site pain, injection site tenderness, and erythema (two patients each); and rash, injection site erythema, injection site induration, and injection site swelling (one patient each)], and hyperuricemia (one patient). ASP0113 was well tolerated in Japanese HCT recipients. Further studies should evaluate its efficacy and safety. ClinicalTrials.gov Identifier: NCT01903928.
巨细胞病毒（CMV）感染/再激活是造血细胞移植（HCT）后的一种严重并发症。DNA疫苗ASP0113包含两个编码CMV抗原（糖蛋白B和包膜磷蛋白65）的质粒，可刺激体液免疫和细胞免疫。2013年6月至2014年2月期间，安斯泰来开展了一项2期、开放标签、非对照、三中心试验，以研究ASP0113在因血液系统疾病接受HCT的日本患者中的安全性和耐受性。招募了10名年龄在22 - 61岁的患者；9名患者接受了至少一剂ASP0113。6名患者在HCT前后间隔接受了全部5剂5mg的ASP0113。允许进行抢先抗病毒治疗。1例患者因原发性疾病复发死亡。所有患者均发生了被认为与ASP0113无关的严重不良事件。7例患者出现CMV病毒血症（通过CMV抗原血症评估），随后接受了抗CMV治疗。没有患者发生CMV终末器官疾病。与ASP0113注射相关的不良事件包括发热（3例患者）、皮肤反应[注射部位疼痛、注射部位压痛和红斑（各2例患者）；皮疹、注射部位红斑、注射部位硬结和注射部位肿胀（各1例患者）]以及高尿酸血症（1例患者）。ASP0113在日本HCT受者中耐受性良好。进一步研究应评估其疗效和安全性。ClinicalTrials.gov标识符：NCT01903928。
