CoVPN 3001 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine SDMC

Project Abstract: 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 Phase3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, andImmunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older."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 HVTN has joined 4 other National Institute ofHealth (NIH) clinical trial networks to form the CoVPN, an enhanced network dedicated to developing globallyeffective vaccines for SARS-CoV-2. Due to its extensive experience implementing HIV vaccine trials, the HIVVaccine Trials Network (HVTN) LOC was selected to as the CoVPN vaccine LOC.This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of mRNA-1273 SARS-CoV-2, a lipid co-formulated messenger ribonucleic acid (mRNA) vaccine encoding the SARS-CoV-2 spike protein(S), to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from clinicaltrial sites across the US, using data analytics to target high risk individuals with a diverse racial and ethnicprofile. In addition, the CoVPN will use accessory community-based sites, staffed by clinical teams from thehome sites and employ mobile clinics to enroll individuals in new high risk settings (e.g., meat packing plants).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 validated assays for diagnosis and immune monitoring.Specific aims of this study are to demonstrate efficacy of mRNA-1273 SARS-CoV-2 to prevent COVID-19, toevaluate the safety and reactogenicity of 2 injections given 28 days apart, the assess the ability to preventinfection with SARS-CoV-2, the assess the ability to modify COVID-19 infection, to evaluate viral infectionkinetics, and to evaluate the vaccine induced immune response. This initial efficacy trial will tell us much aboutthe adaptive immune response in persons who receive a SARS-CoV-2 S protein based vaccine and about theirability to modify the disease course of COVID-19. In addition, it will improve our understanding of the dynamicsand duration of these responses and will inform rational design and testing of preventive and therapeuticmonoclonal antibody interventions. Lastly, the results of this trial will be used to assess registration of thisvaccine product as well as to modify future COVID-19 vaccine trials planned over the next 12 months.