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

FOA：PA-20-272：对现有NIH补助金和合作协议的行政补充 活动代码/奖项：UM1/A1068614-15(家长奖) ---------------------------------- 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“A”的新冠肺炎疫苗效力试验 平行分组，第三阶段，多阶段，改良的双盲，多臂研究，以评估有效性，安全性， 两种SARS-CoV-2佐剂重组蛋白疫苗(单价和双价)的免疫原性 用于预防18岁及以上成年人的新冠肺炎。 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 145个美国(美国)和17个国家的71个国际临床试验地点的医生-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。 这项3期、多阶段、改良的双盲、安慰剂对照、多臂研究将测试疗效， 赛诺菲-巴斯德SARS-CoV2联合AS03佐剂灌流Spike Delta TM的安全性和免疫原性 单价D614(单价疫苗)&带有AS03佐剂的SARS-CoV2灌流Spike Delta TM，双价 D614/B.1.351(双价疫苗)，用于修改18岁及以上成年人的新冠肺炎病。参与者 将从美国和全球各地的临床试验地点招募人员，使用数据分析来瞄准高风险 具有不同种族和民族特征的个人。 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。所有试验终点分析都将使用 用于诊断和免疫监测的合格和有效的检测。 本研究的具体目的是评估正在研究的CoV2 PreDTM重组体的临床疗效 用AS03-单价和双价佐剂(“研究疫苗”)预防幼稚成人的蛋白质 第二次注射后14天出现有症状的新冠肺炎的发生率；以评估研究的安全性 在整个研究过程中将疫苗与安慰剂进行比较；评估在SARS-CoV-2幼稚的参与者中， CoV2 PreDTM-AS03疫苗预防14天后以下并发症的临床效果 第二针：预防SARS-CoV-2感染，预防重症新冠肺炎；描述 SARS-CoV-2非幼稚成人有症状新冠肺炎发作的疾病频度和谱 每一研究组。 这项疗效试验将告诉我们更多关于两种重组疫苗的能力，它们针对的是 常见的SARS-CoV-2变种，诱导强烈的适应性保护反应。在Novavax疫苗之后，这个 是第二个进行疗效测试的大规模重组蛋白疫苗，也是第一个使用 二价疫苗包括令人担忧的B.1.351变种。如果成功，这将是一种重要的疫苗，可以 迅速扩大规模，并在世界各地部署。本次试验的结果将用于评估注册情况 并将提供关键信息，告知新冠肺炎的后代 疫苗。

FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ 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.