CoVPN 3001 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine SDMC

项目摘要 该提案概述了新冠肺炎预防网络疫苗的科学议程 领导运营中心实施首个新冠肺炎疫苗疗效试验A阶段 3、随机、分层、观察者盲、安慰剂对照研究，以评估疗效、安全性和 SARS-CoV-2mRNA-1273疫苗在18岁及以上成人中的免疫原性 随着新冠肺炎的全球流行，我们认识到对修改新冠肺炎的疫苗的重大需求 SARS-CoV-2感染者。为了弥补这一差距，HVTN加入了其他4个国家研究所 健康(NIH)临床试验网络形成CoVPN，这是一个致力于在全球开发的增强型网络 SARS-CoV-2的有效疫苗。由于其实施艾滋病毒疫苗试验的丰富经验，艾滋病毒 选择疫苗试验网络(HVTN)LOC作为CoVPN疫苗LOC。 这项试验是一项第三阶段的双盲安慰剂对照研究，将测试mRNA-1273 SARS-CoV的疗效。 2，编码SARS-CoV-2刺突蛋白的脂质联合信使核糖核酸疫苗 (S)，将新冠肺炎病改良用于18岁及以上的成年人。参与者将从临床招募 美国各地的试验地点，使用数据分析针对不同种族和民族的高危个人 侧写。此外，CoVPN将使用基于社区的附件站点，由来自 并雇用流动诊所将个人纳入新的高风险环境(如肉类加工厂)。 参与者将接受SARS-CoV-2感染的症状筛查，如果他们被感染，将接受 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 进展为中重度新冠肺炎将转诊住院治疗。所有试验终点分析都将是 在CoVPN实验室完成，使用经过验证的检测方法进行诊断和免疫监测。 本研究的具体目的是证明1273mRNA-1273SARS-CoV-2对预防新冠肺炎、 评估两次注射间隔28天的安全性和反应性，评估预防的能力 用SARS-CoV-2感染评估新冠肺炎感染的修饰能力，以评估病毒感染 动力学，并评价疫苗诱导的免疫应答。这项初步的疗效试验将告诉我们更多关于 SARS-CoV-2 S蛋白疫苗接种者的获得性免疫应答及其对机体的影响 能够修改新冠肺炎的病程。此外，它还将提高我们对动态的理解 以及这些反应的持续时间，并将为预防和治疗的合理设计和测试提供信息 单抗干预。最后，这次试验的结果将被用来评估这一 该公司还将继续研发疫苗产品，并修改未来12个月内计划进行的新冠肺炎疫苗试验。

Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the first COVID-19 vaccine efficacy trial “A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older.” 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 HVTN has joined 4 other National Institute of Health (NIH) clinical trial networks to form the CoVPN, an enhanced network dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing HIV vaccine trials, the HIV Vaccine Trials Network (HVTN) LOC was selected to as the CoVPN vaccine LOC. This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of mRNA-1273 SARS-CoV- 2, a lipid co-formulated messenger ribonucleic acid (mRNA) vaccine encoding the SARS-CoV-2 spike protein (S), to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from clinical trial sites across the US, using data analytics to target high risk individuals with a diverse racial and ethnic profile. In addition, the CoVPN will use accessory community-based sites, staffed by clinical teams from the home sites and employ mobile clinics to enroll individuals in new high risk settings (e.g., meat packing plants). 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 at CoVPN laboratories, using validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of mRNA-1273 SARS-CoV-2 to prevent COVID-19, to evaluate the safety and reactogenicity of 2 injections given 28 days apart, the assess the ability to prevent infection with SARS-CoV-2, the assess the ability to modify COVID-19 infection, to evaluate viral infection kinetics, and to evaluate the vaccine induced immune response. This initial efficacy trial will tell us much about the adaptive immune response in persons who receive a SARS-CoV-2 S protein 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 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 planned over the next 12 months.