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COVID-19预防网络（CoVPN）疫苗的科学议程 领导运营中心（COVID-19疫苗有效性试验“A阶段”）的实施 3、随机、分层、观察者设盲、安慰剂对照研究，以评价 mRNA-1273 SARS-CoV-2疫苗在18岁及以上成人中的免疫原性。 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，HVTN加入了其他4个国家研究所， 美国国立卫生研究院（NIH）临床试验网络，以形成CoVPN，这是一个增强型网络，致力于在全球范围内开发 SARS-CoV-2的有效疫苗由于其在实施艾滋病毒疫苗试验方面的丰富经验，艾滋病毒 疫苗试验网络（HVTN）被选为CoVPN疫苗试验网络。 这项试验是一项3期、安慰剂对照、双盲研究，将测试mRNA-1273 SARS-CoV的疗效。 2，编码SARS-CoV-2刺突蛋白的脂质共配制信使核糖核酸（mRNA）疫苗 (S)，以改变18岁及以上成年人的COVID-19疾病。参与者将从临床 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风险个体， profile.此外，CoVPN将使用附属的基于社区的网站，由来自 家庭站点并使用移动的诊所来登记处于新的高风险环境中的个体（例如，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， 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， 发展至中重度COVID-19将被转介住院。所有试验终点分析将 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mRNA-1273 SARS-CoV-2预防COVID-19的有效性， 评价间隔28天注射2次的安全性和反应原性，评估预防 感染SARS-CoV-2，评估修饰COVID-19感染的能力，评估病毒感染 动力学，并评价疫苗诱导的免疫应答。这个初步的疗效试验将告诉我们很多关于 接受基于SARS-CoV-2 S蛋白疫苗的人的适应性免疫应答， 改变COVID-19病程的能力。此外，它将提高我们对动力学的理解 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 单克隆抗体干预。最后，本试验的结果将用于评估本 疫苗产品以及修改未来12个月计划的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 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.