Novavax, Inc, Gaithersburg, Maryland.
Now with Vaccines Clinical Research, Global Clinical Development, Merck Research Laboratories, North Wales, Pennsylvania.
JAMA Netw Open. 2023 Apr 3;6(4):e239135. doi: 10.1001/jamanetworkopen.2023.9135.
Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.
To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.
DESIGN, SETTING, AND PARTICIPANTS: The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.
Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.
Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.
Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.
The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.
ClinicalTrials.gov Identifier: NCT04611802.
COVID-19 病例中有 20%以上和 0.4%的死亡发生在儿童中。在证明了佐剂、重组刺突蛋白疫苗 NVX-CoV2373 在成人中的安全性和有效性后，PREVENT-19 试验立即扩大到青少年。
评估 NVX-CoV2373 在青少年中的安全性、免疫原性和疗效。
设计、地点和参与者：NVX-CoV2373 疫苗在 PREVENT-19 试验的扩展部分中进行了评估，该试验是一项在美国进行的、随机、观察者盲法、安慰剂对照的多中心 III 期临床试验，参与者年龄在 12 至 17 岁之间。参与者于 2021 年 4 月 26 日至 6 月 5 日入组，研究正在进行中。在安全性随访 2 个月后实施了盲法交叉，为所有参与者提供了活性疫苗。主要排除标准包括已知的实验室确诊的 SARS-CoV-2 感染或已知的免疫抑制。在 2304 名符合条件的参与者中，有 57 名被排除，2247 名被随机分组。
参与者随机分为 2:1 接受 2 剂肌内注射 NVX-CoV2373 或安慰剂，间隔 21 天。
与 PREVENT-19 中的年轻成年人（18-25 岁）相比，中和抗体反应的血清学非劣效性、预防实验室确诊的 COVID-19 的保护效力、以及对不良反应和安全性的评估。
在 2232 名参与者（1487 名 NVX-CoV2373 和 745 名安慰剂接受者）中，平均（SD）年龄为 13.8（1.4）岁，1172 名（52.5%）为男性，1660 名（74.4%）为白人个体，359 名（16.1%）在基线时有过 SARS-CoV-2 感染史。接种疫苗后，与年轻成年人相比，青少年中和抗体几何平均滴度的比值为 1.5（95%CI，1.3-1.7）。在中位随访 64（IQR，57-69）天后，发生了 20 例轻度 COVID-19 病例，包括 6 例 NVX-CoV2373 接受者（发病率为 2.90[95%CI，1.31-6.46]每 100 人年）和 14 例安慰剂接受者（发病率为 14.20[95%CI，8.42-23.93]每 100 人年），疫苗效力为 79.5%（95%CI，46.8%-92.1%）。针对 Delta 变异株（通过测序确定的唯一病毒变异株 [n=11]）的疫苗效力为 82.0%（95%CI，32.4%-95.2%）。不良反应主要为轻度至中度且短暂，NVX-CoV2373 第二次给药后趋势更为明显。严重不良事件罕见且在治疗之间平衡。没有不良事件导致研究中止。
这项随机临床试验的结果表明，NVX-CoV2373 在预防 COVID-19 方面是安全、免疫原性和有效的，包括主要的 Delta 变异株，在青少年中。
ClinicalTrials.gov 标识符：NCT04611802。
