CoVPN 3008 - Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern

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疫苗有效性试验的实施， “COVID-19 mRNA疫苗在SARS-CoV-2地区的多中心随机有效性研究 关注的变化”。 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）领导了 快速构建CoVPN，与5个NIH支持的临床试验网络合作， 美国145家临床试验机构和17个国家的71家国际临床试验机构的医生-科学家网络 致力于开发全球有效的SARS-CoV-2疫苗。由于其丰富的经验 在过去的20年里，艾滋病毒疫苗试验网络（HVTN）一直在实施全球艾滋病毒疫苗试验。 被选为CoVPN疫苗试验的实验室。 这项3期、双盲、安慰剂对照、交叉疫苗接种研究将测试 COVID-19祖先株mRNA疫苗在预防COVID-19疾病（无论其严重程度如何）方面， 并在世界各地有严重COVID-19风险的人群中预防COVID-19严重疾病 其中SARS-CoV-2 1.351毒株的流行率很高。 该试验的目的是在世界各地区提供尽可能快速的疗效评估 当地获得有效疫苗的机会有限。受试者将以1：1的比例随机接受 立即或延迟接种疫苗。盲态交叉预期将在疫苗获益时进行。 根据至少50个主要COVID-19终点宣布，预计将累计约3 审判开始后的几个月。所有试验终点测定将使用合格和经验证的诊断测定进行 免疫监测。 本研究的具体目的是证明COVID-19 mRNA（Moderna mRNA-1273）疫苗的有效性 在以下成人中，从第2次给药后14天开始预防病毒学证实的症状性COVID-19 严重COVID-19的风险;评估COVID-19 mRNA疫苗预防严重COVID-19的疫苗效力 在有严重COVID-19风险的成人中，从第2次给药后14天开始;并评估安全性和 COVID-19 mRNA疫苗在有严重COVID-19风险的成年人中的耐受性。 这项有效性试验将告诉我们很多关于mRNA疫苗对抗祖先武汉病毒株的能力。 SARS-CoV-2保护暴露于不同毒株的个体，特别是1.351第一优势毒株 南非的有此外，它将提高我们对这些免疫系统的动态和持续时间的理解。 反应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 在世界上替代菌株继续扩散的地区进行干预。最后，这个结果 试验将用于评估该疫苗产品的注册以及修改未来的COVID-19疫苗 计划在未来12个月内进行审判。

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 “Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern.” 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, observer-blinded, placebo-controlled, crossover-vaccination study will test the efficacy of the COVID-19 ancestral strain mRNA vaccine in preventing COVID-19 disease regardless of severity, and preventing COVID-19 severe disease in people who are at risk for severe COVID-19 in areas of the world where the prevalence of the SARS-CoV-2 1.351 strain is substantial. The trial has been designed to provide as rapid assessment of efficacy as possible in regions of the world where local access to effective vaccines are limited. Subjects will be randomized in a 1:1 ratio to receive immediate or deferred vaccine. The blinded cross-over is expected to take place when vaccine benefit is declared based on at least 50 primary COVID-19 endpoints, anticipated to be accrued approximately 3 months post-trial start. 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 COVID-19 mRNA (Moderna mRNA-1273) vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; to assess vaccine efficacy of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; and to assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19. This efficacy trial will tell us much about ability of an mRNA vaccine against the ancestral Wuhan strain of SARS-CoV-2 to protect individuals exposed to divergent strains, and in particular 1.351 first predominant in South Africa. 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 in parts of the world where alternative strains continue to proliferate. 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.