CoVPN 3008 A Phase 3, Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern

CoVPN 3008 COVID-19 mRNA 疫苗在 SARS-CoV-2 变异关注地区的 3 期、多中心、随机、功效研究

• 批准号: 10493538
• 负责人: Judith S. Currier
• 金额: $ 700.7万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-26 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10493538
• 关键词: 2019-nCoV; AIDS clinical trial group; AIDS/HIV problem; Address; Adult; Affect; Area; Biological Assay; Blinded; COVID-19; COVID-19 pandemic; COVID-19 prevention; COVID-19 severity; COVID-19 vaccine; Cellular Assay; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Cohort Studies; Communicable Diseases; Constitution; Coronavirus; Country; Development; Diagnosis; Disease; Dose; End Point Assay; Exposure to; Eye; Future; HIV Vaccine Trials Network; HIV vaccine; HIV/TB; Health; Hepatitis B; High Prevalence; Immune; Immune response; Immunity; Immunologic Monitoring; Immunology; Individual; Infection; Infection Control; International; Intervention; Knowledge; Laboratories; Malaria; Mediating; Messenger RNA; Moderna COVID-19 vaccine; Morbidity - disease rate; Persons; Phase; Physicians; Placebo Control; Population; Preparation; Prevalence; Prevention; Preventive; Proliferating; Quality Control; RNA vaccine; Randomized; Randomized Clinical Trials; Research Methodology; Risk; SARS-CoV-2 B.1.351; SARS-CoV-2 infection; SARS-CoV-2 variant; Safety; Sampling; Scientist; Serology test; Severities; Site; South Africa; System; Testing; Therapeutic Monoclonal Antibodies; Typhoid Fever; United States; United States National Institutes of Health; Vaccines; Validation; base; clinical trial analysis; design; efficacy evaluation; efficacy study; efficacy testing; efficacy trial; experience; immune function; improved; mortality; prevent; programs; quality assurance; rational design; response; severe COVID-19; symptomatic COVID-19; vaccine efficacy; vaccine trial; variants of concern

Abstract: 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, observer-blinded, placebo-controlled, crossover-vaccination study will test the efficacy of the COVID-19 ancestral strain mRNA vaccine in preventing COVID-19 disease regardless of severity, and preventing COVID-19 severe disease in people who are at risk for severe COVID-19 in areas of the world where the prevalence of the SARS-CoV-2 1.351 strain is substantial. The trial has been designed to provide as rapid assessment of efficacy as possible in regions of the world where local access to effective vaccines are limited. Subjects will be randomized in a 1:1 ratio to receive immediate or deferred vaccine. The blinded cross-over is expected to take place when vaccine benefit is declared based on at least 50 primary COVID-19 endpoints, anticipated to be accrued approximately 3 months post-trial start. 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 COVID-19 mRNA (Moderna mRNA-1273) vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; to assess vaccine efficacy of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; and to assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19. This efficacy trial will tell us much about ability of an mRNA vaccine against the ancestral Wuhan strain of SARS-CoV-2 to protect individuals exposed to divergent strains, and in particular 1.351 first predominant in South Africa. 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 in parts of the world where alternative strains continue to proliferate. 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.

摘要：随着全球Covid-19的大流行，我们认识到对SARS-COV-2感染个体中COVID-19的疫苗的重要需求。在解决这一差距方面，美国国立卫生研究院（NIH）领导了COVPN的快速宪法，与5个NIH支持临床试验网络，建立了在美国145（美国）（美国）和71个国际临床试验网站的增强网络，并在17个国家 /地区建立了71个国际临床试验地点，该网站致力于为SARS-COV-2开发全球有效的疫苗。由于其在过去20年中实施全球HIV疫苗试验的丰富经验，因此选择了HIV疫苗试验网络（HVTN）LOC作为COVPN疫苗试验的LOC。这项第3阶段，观察者盲，安慰剂控制的，交叉疫苗接种研究将测试COVID-19祖先菌株mRNA疫苗在防止Covid-19疾病中的疗效，无论严重程度如何，并防止COVID-19的严重疾病在严重的菌株中处于严重菌株的风险中，在SARS-COV的范围内，这是严重的Covid-nercial sars-sars-cov eart sars-cov eart sars-cov eart sars-cov eart sars-cov。该试验的设计目的是在当地获得有效疫苗的世界区域中尽可能快速评估疗效。受试者将以1：1的比率随机分配，以接收立即或递延疫苗。预计将根据至少50个原发性终点宣布疫苗益处，预计将在审判后大约3个月进行宣布，预计将进行盲目交叉。所有试验终点测定法都将使用合格的和经过验证的测定法进行诊断和免疫监测。这项研究的具体目的是证明Covid-19 mRNA（ModernA mRNA-1273）疫苗的功效，以防止在剂量2后14天后，在患有严重互联-19风险的成年人中，从病毒学确认的有症状性covid-19开始。评估Covid-19 mRNA疫苗的疫苗疗效，以防止剂量2后14天，在面临严重covid-19的风险的成年人中，从剂量2开始后开始进行严重的covid-19；并评估在患有严重COVID-19的成年人中，共vid-19-19 mRNA疫苗的安全性和耐受性。这项功效试验将向我们介绍mRNA疫苗对SARS-COV-2祖先武汉菌株的能力，以保护暴露于发散菌株的个体，尤其是1.351南非的首次占主导地位。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，并将为有理设计和测试预防性和治疗性单克隆抗体干预措施的测试，这些抗体干预措施继续替代菌株继续繁殖。最后，该试验的结果将用于评估该疫苗产品的注册，并修改未来12个月计划的未来Covid-19疫苗试验。