CoVPN 3005 - Efficacy, Immunogenicity, and Safety of Two SARS-CoV-2 Recombinant Protein Vaccines with Adjuvant in Adults 18 Years of Age and Older

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，名为“A 平行组、III期、多阶段、改良双盲、多组研究，以评估疗效、安全性， 两种SARS-CoV-2重组蛋白疫苗（单价和双价）的免疫原性 用于18岁及以上成年人预防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）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III期、多阶段、改良双盲、安慰剂对照、多组研究将测试 赛诺菲-巴斯德SARS-CoV 2融合前Spike delta TM与AS 03有效性、安全性和免疫原性 佐剂，单价D 614（单价疫苗）& SARS-CoV 2 prefusion Spike delta TM with AS 03 佐剂，二价D 614/B.1.351（二价疫苗），用于在18岁的成人中修饰COVID-19疾病， 老了参与者将使用数据分析从美国和全球的临床试验中心招募 针对不同种族和民族的高危人群。 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， 发展至中重度COVID-19将被转介住院。所有试验终点分析将 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评估研究性CoV 2 preS dTM重组体的临床疗效 在初次接种的成人中使用AS 03佐剂的蛋白质-单价和二价（“研究疫苗”）， 预防第二次注射后> 14天出现的症状性COVID-19;评估安全性 在整个研究过程中，与安慰剂相比，研究疫苗的有效性;在SARS受试者中， CoV-2初治，CoV 2 preS dTM-AS 03疫苗预防以下疾病的临床有效性 发生在第二次注射后> 14天：预防SARS-CoV-2感染，预防严重 COVID-19;描述有症状的COVID-19发作中的疾病频率和谱， 每个研究组中的SARS-CoV-2非初治成人。 这项有效性试验将告诉我们两种重组疫苗的能力，靶向两种 最常见的SARS-CoV-2变体，以诱导强适应性保护反应。Novavax之后 疫苗，这是第二个大规模的重组蛋白疫苗进行有效性测试，这是第一个 试验使用包括B.1.351变异的二价疫苗。如果成功，这将是一个重要的 这种疫苗可以迅速扩大规模并在全世界部署。这项试验的结果将用于 评估该疫苗产品的注册情况，并提供重要信息， 新型冠状病毒疫苗。

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 parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age 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 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, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally 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 assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS- CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines.