CoVPN 3003 A Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older LC 3

项目摘要 该提案概述了COVID-19预防网络（CoVPN）疫苗领导层的科学议程 运营中心（COVID-19）实施名为“一个随机， 一项评估Ad26.COV2.S治疗糖尿病的疗效和安全性的双盲、安慰剂对照、III期研究 在18岁及以上的成年人中预防SARS-CoV-2介导的COVID-19。 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）迅速 CoVPN的组成，与5个NIH支持的临床试验网络合作，以创建一个增强的网络， 美国64家临床试验机构和15个国家的55家国际临床试验机构的医生-科学家致力于 研发全球有效的SARS-CoV-2疫苗。由于其在实施全球 过去20年的艾滋病毒疫苗试验，艾滋病毒疫苗试验网络（HVTN）LOC被选为LOC 用于CoVPN疫苗试验 这项3期、安慰剂对照、双盲研究将测试Ad26.COV2.S的疗效， 复制缺陷型腺病毒26型（Ad 26）载体，构建用于编码严重急性呼吸道感染 综合征冠状病毒-2（SARS-CoV-2）刺突（S）蛋白修饰18岁成人COVID-19疾病 年纪也更大了参与者将从美国、拉丁美洲和南美洲的临床试验中心招募。 非洲使用数据分析来针对具有不同种族和民族特征的高风险个体。 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， 中重度COVID-19患者将被转诊住院。将进行所有试验终点分析 使用合格和经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Ad26.COV2.S预防COVID-19的有效性，评估 1 × 1011病毒颗粒（VP）或安慰剂单次肌内（IM）注射的安全性、耐受性和反应原性， 评估预防SARS-CoV-2感染的能力，评估改变COVID-19疾病的能力， 评估预防急诊室就诊的能力，并评估结合和中和抗体 应答这项疗效试验将告诉我们很多关于接受免疫治疗的人的适应性免疫反应。 基于SARS-CoV-2 S蛋白的疫苗及其改变COVID-19病程的能力。在 此外，它将提高我们对这些免疫反应的动态和持续时间的理解， 为预防性和治疗性单克隆抗体干预措施的合理设计和测试提供信息。最后 该试验的结果将用于评估该疫苗产品的注册情况，并用于修改未来的COVID-19。 计划在未来12个月内进行19次疫苗试验。

Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 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 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 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 phase 3, placebo-controlled, double-blinded study will test the efficacy of Ad26.COV2.S, a recombinant, replication-incompetent adenovirus type 26 (Ad26) vector constructed to encode the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from clinical trial sites across the US, Latin America and South Africa 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 using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of Ad26.COV2.S to prevent COVID-19, to evaluate the safety, tolerability and reactogenicity of one intramuscular (IM) injection of 1x1011 viral particles (vp) or placebo, 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 immune 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.