Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.
Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.
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DOI：
10.1056/nejmoa2202261
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发表时间：
2022-06-02
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ZF2001疫苗含有严重急性呼吸综合征冠状病毒2型受体结合结构域的二聚体形式和氢氧化铝作为佐剂，在1期和2期临床试验中被证明是安全的，具有可接受的副作用，并且在成人中具有免疫原性。我们进行了一项随机、双盲、安慰剂对照的3期试验，以调查ZF2001的疗效并确认其安全性。该试验在乌兹别克斯坦、印度尼西亚、巴基斯坦和厄瓜多尔的31个临床中心进行；另外一个在中国的中心只被包括在安全分析中。成年参与者（≥18岁）按1:1的比例随机分配，共接受3次25 μg剂量的ZF2001或安慰剂（间隔30天）。主要终点是在接受第三剂疫苗后至少7天内，聚合酶链反应试验证实出现症状性2019冠状病毒病（Covid-19）。一个关键的次要疗效终点是在接受第三剂后至少7天发生严重至危重型Covid-19（包括Covid-19相关死亡）。在2020年12月12日至2021年12月15日期间，共有28,873名参与者接受了至少一剂ZF2001或安慰剂，并被纳入安全性分析；完成三剂量方案的25193名参与者，随访数据约为6个月，被纳入更新的主要疗效分析，该分析于2021年12月15日的第二个数据截止日期进行。在最新的分析中，ZF2001组12,625名参与者中有158人报告了主要终点病例，安慰剂组12,568名参与者中有580人报告了主要终点病例，疫苗有效性为75.7%（95%可信区间[CI]， 71.0至79.8）。ZF2001组中有6名参与者出现重症至危重型Covid-19，安慰剂组中有43名参与者出现重症至危重型Covid-19，疫苗效力为87.6% (95% CI， 70.6至95.7)；在疫苗效力为86.5% （95% CI， 38.9至98.5）的情况下，2名和12名参与者分别发生了与covid -19相关的死亡。在两组中，不良事件和严重不良事件的发生率是平衡的，没有疫苗相关的死亡。绝大多数不良反应（98.5%）为1级或2级。在一个大型成人队列中，ZF2001疫苗被证明在完全接种疫苗后至少6个月内对有症状和严重至危重型Covid-19是安全有效的。（国家科技重大专项等资助；ClinicalTrials.gov编号：NCT04646590）
The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19–related death) at least 7 days after receipt of the third dose. Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19–related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.)