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 该提案概述了新冠肺炎预防网络疫苗领导的科学议程 运营中心(LOC)，用于实施新冠肺炎疫苗效力试验， 3期双盲安慰剂对照研究评估Ad26.COV2.S治疗慢性阻塞性肺疾病的疗效和安全性 预防SARS-CoV-2介导的18岁及以上成人新冠肺炎. 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)牵头开展了快速 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 医生-科学家在美国和15个国家和地区的55个国际临床试验地点致力于 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的20年里，艾滋病毒疫苗试验网络(HVTN)LOC被选为LOC 用于CoVPN疫苗试验。 这个阶段3，安慰剂对照的双盲研究将测试Ad26.COV2.S，一种重组的， 构建非复制性腺病毒26型(AD26)载体编码严重急性呼吸道综合征 SARS冠状病毒2型尖峰蛋白(S)修饰18岁成人新冠肺炎病 而且年纪也更大。参与者将从美国、拉丁美洲和南美的临床试验地点招募 非洲使用数据分析针对具有不同种族和民族特征的高危个人。 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。进展中的感染者 至中重度新冠肺炎将转诊住院治疗。将完成所有试验终点分析 使用合格和有效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预防新冠肺炎的有效性，评估 肌肉注射1x1011病毒颗粒(VP)或安慰剂的安全性、耐受性和反应性， 评估预防感染SARS-CoV-2的能力，评估修改新冠肺炎疾病的能力， 评估预防急诊室就诊的能力，并评估结合抗体和中和抗体 回应。这项疗效试验将告诉我们更多关于接受疫苗的人的获得性免疫反应 关于SARS-CoV-2 S蛋白疫苗及其对新冠肺炎病程的修改能力。在……里面 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，并将 告知预防性和治疗性单抗干预措施的合理设计和测试。最后， 这项试验的结果将用于评估该疫苗产品的注册情况，以及修改未来的COVID- 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.