CoVPN 3004 A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Immunogenicity of a SARS-CoV-2 Spike Protein Nanoparticle Vaccine in Adults

项目摘要 该提案概述了COVID-19预防网络（CoVPN）疫苗领导层的科学议程 运营中心（COVID-19）负责实施名为“第3阶段， 一项随机化、观察者设盲、安慰剂对照研究，评价 SARS-CoV-2重组刺突蛋白纳米粒疫苗的免疫原性研究 使用Matrix-M™佐剂治疗≥ 18岁成人受试者。” 随着全球COVID-19大流行，我们认识到对修饰COVID-19的疫苗的巨大需求， SARS-CoV-2感染者。为了解决这一差距，美国国立卫生研究院（NIH）迅速 CoVPN的组成，与5个NIH支持的临床试验网络合作，以创建一个增强的网络， 美国145个临床试验中心和17个国家的71个国际临床试验中心的医生-科学家，致力于 研发全球有效的SARS-CoV-2疫苗。由于其在实施全球 过去20年的艾滋病毒疫苗试验，艾滋病毒疫苗试验网络（HVTN）LOC被选为LOC 用于CoVPN疫苗试验 这项3期、安慰剂对照、双盲研究将测试一种抗肿瘤药物的疗效、安全性和免疫原性。 SARS CoV-2 rS，一种与Matrix-M佐剂一起施用的纳米颗粒疫苗，分两次施用21天 除此之外，还可以改变18岁及以上成年人的COVID-19疾病。期间接受安慰剂的受试者 初始随机化将在揭盲时接种疫苗。所有参与者将获得第三次加强剂量， 在完成原始方案后8个月内。将从临床试验中心招募受试者， 美国和全球使用数据分析来针对具有不同种族和民族特征的高风险个体。 参与者将接受SARS-CoV-2感染的症状筛查，如果他们被感染， 通过频繁的临床检查和远程监测生命体征进行监测。受感染的人， 中重度COVID-19患者将被转诊住院。所有试验终点分析将使用 用于诊断和免疫监测的合格和经验证的测定。 本研究的具体目的是证明SARS-CoV-2 rS疫苗预防SARS-CoV-2的有效性 感染和COVID-19疾病;评估其在种族、民族、高风险与低风险人口统计学中的影响 评价结合和中和抗体应答;评价免疫应答的持久性; 评估疫苗安全性;评估两组的全因死亡率;并进行卫生经济学研究 成果研究（HEOR）。这项疗效试验将告诉我们很多关于适应性免疫反应的信息， 接受SARS-CoV-2 rS纳米颗粒疫苗的人，以及他们改变疾病的能力 COVID-19的过程。此外，它将提高我们对这些免疫系统的动态和持续时间的理解。 并将为预防性和治疗性单克隆抗体的合理设计和测试提供信息 干预措施。最后，该试验的结果将用于评估该疫苗产品的注册以及 修改未来的COVID-19疫苗试验。

Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) with Matrix-M™ Adjuvant in Adult Participants ≥ 18 years.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, placebo-controlled, observer-blinded study will test the efficacy, safety and immunogenicity of a SARS CoV-2 rS, a nanoparticle vaccine administered with Matrix-M adjuvant administered in two doses 21 days apart, to modify COVID-19 disease in adults 18 years of age and older. Participants who receive placebo during original randomization will receive vaccine at unblinding. All participants will be offered a 3rd booster dose no than 8 months after completing the original regimen. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of SARS-CoV-2 rS vaccine to prevent SARS-CoV-2 infection and COVID-19 disease; to evaluate its effect across race, ethnicity, high-risk vs. low-risk demographic groups; to evaluate binding and neutralizing antibody responses; to evaluate the durability of immune responses; to assess the vaccine safety; to assess all-cause mortality in the two groups; and to perform health economics and outcomes research (HEOR). This efficacy trial will tell us much about the adaptive immune response in persons who receive a SARS-CoV-2 rS nanoparticle-based vaccine and about their ability to modify the disease course of COVID-19. In addition, it will improve our understanding of the dynamics and duration of these immune responses and will inform rational design and testing of preventive and therapeutic monoclonal antibody interventions. Lastly, the results of this trial will be used to assess registration of this vaccine product as well as to modify future COVID-19 vaccine trials.