Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site: CoVPN 3004

项目总结/摘要 马里兰州大学医学院（UMSOM）疫苗开发和全球健康中心 (CVD)自1974年以来一直是VTEU网站。VTEU的目标是提出创新概念 进行临床研究，并实施临床研究中心方案，以评估疫苗、其他预防性生物制剂， 用于治疗和预防传染病的治疗剂、诊断剂和装置，并且CVD是 为实现这一目标做好了独一无二的准备。CVD的专家和有成就的调查团队已经 在解决NIAID优先领域所需的所有领域的互补技能组合， 管理层计划有效分配工作，同时开展多个项目。过去17 几个月来，NIAID感兴趣的一个关键领域是发现安全有效的保护措施， 包括疫苗，用于有感染COVID-19风险的人。本提案介绍了一项关键的 竞技场方案，即Novavax 3期关键疗效研究的儿科扩展 重组刺突蛋白疫苗与M基质佐剂。该项目的主要目标是（1）评估 与安慰剂相比，用基质-M1佐剂的SARS-CoV-2 rS的2次给药方案对 在完成第二次注射后≥ 7天诊断为PCR证实的症状性COVID-19疾病， 12至< 18岁的青少年参与者的初始疫苗接种;以及（2）描述 基于以下因素，青少年受试者（12至<18岁）中疫苗与安慰剂的安全性经验 每次接种后7天（第0天和第21天），按毒性等级列出的征集性短期反应原性， 第一次接种疫苗。还对多个其他目标进行了评估。该设计是第三阶段， 一项随机、双盲、安慰剂对照研究，旨在评价 SARS-CoV-2 rS与Matrix-M1佐剂在≥ 18岁成人受试者中的应用（成人主研究）， 儿科扩展（本提案适用于儿科扩展）。在儿科扩展中， 年龄在12至17岁之间的参与者将被招募而不分层。参与者被跟踪2年， 安全性、耐受性、功效和免疫应答。预期样本量为3000例青少年：2000例 先接种疫苗，1000人先接种安慰剂。6个月后，将进行双盲交叉 结束了这项研究预计将提供必要的数据，使该疫苗在12至 17岁的美国人

Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD’s expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. In the past 17 months, a key area of interest at NIAID has been discovery of safe and effective protective measures, including vaccines, for persons at risk of COVID-19. This proposal describes the implementation of a critical protocol in that arena, namely the Pediatric expansion of the phase 3 pivotal efficacy study of the Novavax recombinant spike protein vaccine with M Matrix adjuvant. The project’s primary objectives are (1) to evaluate the efficacy of a 2-dose regimen of SARS-CoV-2 rS adjuvanted with Matrix-M1 compared to placebo against PCR-confirmed symptomatic COVID-19 illness diagnosed ≥ 7 days after completion of the second injection in the initial set of vaccinations of adolescent participants 12 to < 18 years of age; and (2) to describe the safety experience for the vaccine versus placebo in adolescent participants (12 to <18 years of age) based on solicited short-term reactogenicity by toxicity grade for 7 days following each vaccination (Days 0 and 21) after the initial set of vaccinations. Multiple additional objectives are also being evaluated. The design is a Phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants ≥ 18 years of age (Adult Main Study) with a Pediatric Expansion (This proposal is for the Pediatric Expansion). In the Pediatric Expansion, adolescent participants 12 to 17 years of age will be enrolled without stratification. Participants are followed for 2 years for safety, tolerability, efficacy, and immune responses. The expected sample size will be 3000 adolescents: 2000 will receive vaccine first and 1000 will receive placebo first. After 6 months, there will be a double-blind cross over. This study is expected to contribute the data necessary to allow for authorization of this vaccine in 12 to 17 year-olds in the US.