CoVPN 3004 A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Immunogenicity of a SARS-CoV-2 Spike Protein Nanoparticle Vaccine in Adults

CoVPN 3004 一项 3 期随机、观察者盲法、安慰剂对照研究，旨在评估成人 SARS-CoV-2 刺突蛋白纳米颗粒疫苗的功效、安全性和免疫原性

• 批准号: 10581423
• 负责人: Peter B. Gilbert
• 金额: $ 23.49万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-29 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581423
• 关键词: 18 year old; 2019-nCoV; Address; Adjuvant; Adult; Antibodies; Antibody Response; Binding; Biological Assay; Biometry; Blinded; COVID-19; COVID-19 Prevention Network; COVID-19 outbreak; COVID-19 pandemic; COVID-19 screening; COVID-19 severity; COVID-19 vaccine; Cells; Cellular Assay; Characteristics; Clinical; Clinical Trials; Clinical Trials Network; Cohort Studies; Communicable Diseases; Constitution; Coronavirus; Country; Data Analytics; Development; Diabetes Mellitus; Diagnosis; Disease; Dose; End Point Assay; Ethnic Origin; Eye; Follow-Up Studies; Future; Goals; HIV Vaccine Trials Network; HIV vaccine; Health; Hospitalization; Hypertension; Immune; Immune response; Immunity; Immunologic Monitoring; Immunology; Individual; Infection Control; International; Intervention; Knowledge; Laboratories; Lead; Leadership; Malaria; Mediating; Monitor; Morbidity - disease rate; Novavax COVID-19 vaccine; Obesity; Outcomes Research; Participant; Persons; Phase; Physicians; Placebo Control; Placebos; Population; Preparation; Prevention; Preventive; Proteins; Protocols documentation; Quality Control; RS protein; Race; Randomized; Randomized Clinical Trials; Recombinants; Regimen; Research Methodology; Risk; SARS-CoV-2 antibody; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Safety; Sampling; Scientist; Serology test; Severity of illness; Site; System; Testing; Therapeutic Monoclonal Antibodies; Typhoid Fever; United States; United States National Institutes of Health; Vaccination; Vaccines; Validation; Virus; adaptive immune response; base; booster vaccine; clinical trial analysis; design; efficacy evaluation; efficacy study; efficacy testing; efficacy trial; experience; health economics; high risk; immune function; immunogenicity; improved; mortality; nanoparticle; neutralizing antibody; operation; placebo controlled study; prevent; programs; quality assurance; racial and ethnic; racial diversity; rational design; recruit; remote monitoring; response; severe COVID-19; symptomatic COVID-19; vaccine efficacy; vaccine safety; vaccine trial

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 Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) with Matrix-M™ Adjuvant in Adult Participants ≥ 18 years.” 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, placebo-controlled, observer-blinded study will test the efficacy, safety and immunogenicity of a SARS CoV-2 rS, a nanoparticle vaccine administered with Matrix-M adjuvant administered in two doses 21 days apart, to modify COVID-19 disease in adults 18 years of age and older. Participants who receive placebo during original randomization will receive vaccine at unblinding. All participants will be offered a 3rd booster dose no than 8 months after completing the original regimen. 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 demonstrate efficacy of SARS-CoV-2 rS vaccine to prevent SARS-CoV-2 infection and COVID-19 disease; to evaluate its effect across race, ethnicity, high-risk vs. low-risk demographic groups; to evaluate binding and neutralizing antibody responses; to evaluate the durability of immune responses; to assess the vaccine safety; to assess all-cause mortality in the two groups; and to perform health economics and outcomes research (HEOR). This efficacy trial will tell us much about the adaptive immune response in persons who receive a SARS-CoV-2 rS nanoparticle-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.

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 (LOC) 负责实施题为“A Phase 3, 随机、观察者盲法、安慰剂对照研究，评估疗效、安全性和 SARS-CoV-2 重组刺突蛋白纳米颗粒疫苗 (SARS-CoV-2 rS) 的免疫原性 在 18 岁以上的成年参与者中使用 Matrix-M™ 佐剂。” 随着全球 COVID-19 大流行，我们认识到对改变 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) 迅速领导了 CoVPN 的组成，与 5 个 NIH 支持的临床试验网络合作，创建一个增强的网络 145 个美国 (US) 和 17 个国家的 71 个国际临床试验中心的医师科学家致力于 开发全球有效的 SARS-CoV-2 疫苗。由于其丰富的全球实施经验 过去 20 年的 HIV 疫苗试验，HIV 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、观察者盲法研究将测试一种药物的功效、安全性和免疫原性。 SARS CoV-2 rS，一种纳米颗粒疫苗，与 Matrix-M 佐剂一起服用，分两剂，21 天 除此之外，还可以改变 18 岁及以上成年人的 COVID-19 疾病。期间接受安慰剂的参与者 最初的随机分组将在揭盲时接受疫苗。所有参与者将获得第三次加强剂量 完成原始治疗方案后 8 个月以上。参与者将从各地的临床试验地点招募 美国和全球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 感染症状筛查，如果被感染，将接受 通过频繁的临床检查和生命体征的远程监测进行监测。进展的感染者 中度至重度的 COVID-19 将被转诊住院治疗。所有试验终点测定将使用 用于诊断和免疫监测的合格且经过验证的检测。 本研究的具体目的是证明 SARS-CoV-2 rS 疫苗预防 SARS-CoV-2 的功效 感染和 COVID-19 疾病；评估其对种族、民族、高风险与低风险人群的影响 团体；评估结合和中和抗体反应；评估免疫反应的持久性； 评估疫苗的安全性；评估两组的全因死亡率；并进行卫生经济学 和结果研究（HEOR）。这项功效试验将告诉我们很多关于适应性免疫反应的信息 接受 SARS-CoV-2 rS 纳米颗粒疫苗的人及其改变疾病的能力 COVID-19 的病程。此外，它将提高我们对这些免疫的动态和持续时间的理解 反应并将为预防性和治疗性单克隆抗体的合理设计和测试提供信息 干预措施。最后，该试验的结果将用于评估该疫苗产品的注册以及 修改未来的 COVID-19 疫苗试验。