CoVPN 3002 - A Phase III Randomized, Double-Blind, Placebo-Controlled Multicenter Study in Adults to Determine the safety, Efficacy, and Immunogenicity of AZD1222 for Prevention of Covid-19

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 III成人随机、双盲、安慰剂对照多中心研究，以确定安全性、有效性、 非复制型ChAdOx1载体疫苗AZD1222的免疫原性研究 新冠肺炎就是这样的。 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，国家卫生研究所(NIH)领导了RAPID CoVPN的组成，与NIH支持的5个临床试验网络合作，以创建一个增强的 在美国和15个国家的55个国际临床试验地点的内科科学家致力于 开发全球有效的SARS-CoV-2疫苗。由于其广泛的全球实施经验 艾滋病毒疫苗试验在过去20年中，艾滋病毒疫苗试验网络(HVTN)LOC被选为 用于CoVPN疫苗试验的LoC。 这项试验是一项第三阶段的双盲安慰剂对照研究，将测试重组人AZD1222的疗效。 表达SARS-CoV-2刺突(S)表面糖蛋白的复制缺陷黑猩猩腺病毒 改良新冠肺炎病适用于18岁及以上的成年人。参与者将从最多100人中招募 美国各地的临床试验站点，使用数据分析针对不同种族和性别的高危个人 种族特征。 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，使用合格和经过验证的分析进行诊断和免疫监测。 本研究的具体目的是证明AZD1222预防新冠肺炎的有效性，评价 间隔4周的2次注射的安全性、耐受性和反应性，以评估预防的能力 感染SARS-CoV-2，评估修改新冠肺炎疾病的能力，评估预防能力 急诊室就诊，并评估结合和中和抗体反应。这项疗效试验将 告诉我们更多关于接受SARS-CoV-2 S蛋白疫苗的人的获得性免疫反应 疫苗和他们改变新冠肺炎病程的能力。此外，它还将改善我们的 了解这些响应的动态和持续时间，并将为合理设计和测试 预防性和治疗性的单抗干预。最后，这项试验的结果将用于 评估该疫苗产品的注册情况，并修改计划于 接下来的12个月。

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 III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19.” 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 Institute 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 64 United States (US) and 55 international clinical trial sites in 15 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 trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of AZD1222, a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein, to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from up to 100 clinical trial sites across the US, 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 at CoVPN laboratories, using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of AZD1222 to prevent COVID-19, to evaluate the safety, tolerability and reactogenicity of 2 injections given 4 weeks apart, to assess the ability to prevent infection with SARS-CoV-2, to assess the ability to modify COVID-19 disease, to assess the ability to prevent emergency room visits, and to evaluate the binding and neutralizing antibody responses. This 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.