CoVPN 3002 A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222 for the Prevention of COVID-19 LAB

This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) VaccinesLeadership Operations Center (LOC) for implementation of the first COVID-19 vaccine efficacy trial "A PhaseIII Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy,and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19."With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 inSARS-CoV-2 infected individuals. Addressing this gap, the National Institute of Health (NIH) led rapidconstitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network ofphysician scientists at 64 United States (US) and 55 international clinical trial sites in 15 countries dedicated todeveloping globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing globalHIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as theLOC for CoVPN vaccine trials.This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of AZD1222, a recombinantreplication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein, tomodify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from up to 100clinical trial sites across the US, using data analytics to target high risk individuals with a diverse racial andethnic profile.Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will bemonitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals whoprogress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will bedone at CoVPN laboratories, using qualified and validated assays for diagnosis and immune monitoring.Specific aims of this study are to demonstrate efficacy of AZD1222 to prevent COVID-19, to evaluate thesafety, tolerability and reactogenicity of 2 injections given 4 weeks apart, to assess the ability to preventinfection with SARS-CoV-2, to assess the ability to modify COVID-19 disease, to assess the ability to preventemergency room visits, and to evaluate the binding and neutralizing antibody responses. This efficacy trial willtell us much about the adaptive immune response in persons who receive a SARS-CoV-2 S protein basedvaccine and about their ability to modify the disease course of COVID-19. In addition, it will improve ourunderstanding of the dynamics and duration of these responses and will inform rational design and testing ofpreventive and therapeutic monoclonal antibody interventions. Lastly, the results of this trial will be used toassess registration of this vaccine product as well as to modify future COVID-19 vaccine trials planned over thenext 12 months.