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 该提案概述了新冠肺炎预防网络疫苗的科学议程 领导运营中心(LOC)实施名为 新冠肺炎基因疫苗在SARS-CoV-2流行地区的多中心随机效力研究 各种令人担忧的问题。 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。为了解决这一差距，美国国立卫生研究院(NIH)牵头 快速建立CoVPN，与NIH支持的5个临床试验网络合作，创建增强的 在美国的145个和17个国家的71个国际临床试验地点的内科-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，实施全球艾滋病毒疫苗试验，艾滋病毒疫苗试验网络(HVTN)LOC 被选为CoVPN疫苗试验的LOC。 这项第三阶段、观察者盲法、安慰剂对照、交叉接种的研究将测试 新冠肺炎祖株基因疫苗在预防新冠肺炎病中的作用 预防新冠肺炎严重疾病在世界各地有严重新冠肺炎风险的人 SARS-CoV-2 1.351毒株大量流行的地方。 这项试验的目的是在世界各地尽可能快速地评估疗效 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 立即或延期接种疫苗。盲目交叉预计将发生在疫苗效益为 基于至少50个主要新冠肺炎端点宣布，预计将累积约3 审判开始后几个月。所有试验终点分析将使用合格和有效的诊断分析方法进行 和免疫监测。 本研究的具体目的是证明新冠肺炎基因疫苗的效力。 预防病毒学确诊的症状新冠肺炎在服用2剂后14天开始治疗 严重新冠肺炎的风险；评估新冠肺炎基因疫苗预防严重新冠肺炎的疫苗效果 对有严重新冠肺炎风险的成年人在接种2剂后14天开始；并评估安全性和 新冠肺炎基因疫苗在有严重新冠肺炎风险的成年人中的耐受性。 这项药效试验将告诉我们更多关于基因疫苗对抗原始武汉株的能力。 保护接触过不同毒株的个人，特别是1.351首个主要病株 在南非。此外，它还将提高我们对这些免疫的动态和持续时间的理解 并将为预防性和治疗性单抗的合理设计和测试提供信息 在世界上另类毒株继续激增的部分地区进行干预。最后，这一结果 试验将用于评估该疫苗产品的注册情况以及修改未来的新冠肺炎疫苗 试验计划在接下来的12个月内进行。

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.