痘病毒载体巨细胞病毒疫苗预防移植受者巨细胞病毒血症：一项 2 期、随机临床试验。
Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.
机构信息
City of Hope Comprehensive Cancer Center, Duarte, California (I.A., L.F., A.N., M.M.A., R.N.).
City of Hope Comprehensive Cancer Center and the Beckman Research Institute of City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., N.H., S.F., D.J.D.).
出版信息
Ann Intern Med. 2020 Mar 3;172(5):306-316. doi: 10.7326/M19-2511. Epub 2020 Feb 11.
BACKGROUND
Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT).
OBJECTIVE
To determine the safety and efficacy of Triplex.
DESIGN
First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933).
SETTING
3 U.S. HCT centers.
PARTICIPANTS
102 CMV-seropositive HCT recipients at high risk for CMV reactivation.
INTERVENTION
Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens.
MEASUREMENTS
The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection.
RESULTS
A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients.
LIMITATION
The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial.
CONCLUSION
No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.
PRIMARY FUNDING SOURCE
National Cancer Institute and Helocyte.
背景
三联疫苗旨在增强巨细胞病毒（CMV）特异性 T 细胞，并在造血干细胞移植（HCT）后早期预防 CMV 再激活。
目的
确定 Triplex 的安全性和疗效。
设计
首例患者、2 期试验。（ClinicalTrials.gov：NCT02506933）。
地点
美国 3 个 HCT 中心。
参与者
102 名 CMV 阳性、HCT 后 CMV 再激活风险高的患者。
干预措施
在 HCT 后 28 天和 56 天给予 Triplex 或安慰剂的肌肉内注射。Triplex 是一种表达免疫显性 CMV 抗原的重组减毒痘病毒（改良安卡拉痘苗）。
测量
主要结局为 CMV 事件（CMV DNA 水平≥1250 IU/mL、CMV 病毒血症需要抗病毒治疗或终末器官疾病）、非复发死亡率和严重（3 级或 4 级）移植物抗宿主病（GVHD），所有这些均在 HCT 后 100 天内评估，接种后 2 周内发生的 3 级或 4 级不良事件（AE）可能或肯定归因于注射。
结果
共有 102 名患者（每组 51 名）接受了第一次接种，91 名（89.2%）接受了两次接种（46 名 Triplex 和 45 名安慰剂）。5 名 Triplex（9.8%）和 10 名安慰剂（19.6%）受者发生 CMV 再激活（危险比，0.46[95%CI，0.16 至 1.4]；P=0.075）。在头 100 天内，没有 Triplex 受者因非复发原因死亡，也没有严重的 AE，接种后 2 周内没有观察到与接种相关的 3 级或 4 级 AE。两组之间注射后严重急性 GVHD 的发生率相似（危险比，1.1[CI，0.53 至 2.4]；P=0.23）。与安慰剂组相比，Triplex 组的 pp65 特异性 T 细胞的长期、效应记忆表型的水平显著升高。
局限性
安慰剂组 CMV 事件的发生率低于预期，降低了试验的效力。
结论
未发现疫苗相关的安全性问题。Triplex 引发并放大了 CMV 特异性免疫反应，接受 Triplex 疫苗接种的患者 CMV 病毒血症较少。
主要资金来源
美国国立癌症研究所和 Helocyte。
Zotero 插件