CoVPN 3004 - 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 LOC

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NOSI: NOT-AI-20-034 FOA: PA-20-135 – Emergency Competitive Revision to Existing NIH Awards 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 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.