Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site: CoVPN 3004

Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. In the past 17 months, a key area of interest at NIAID has been discovery of safe and effective protective measures, including vaccines, for persons at risk of COVID-19. This proposal describes the implementation of a critical protocol in that arena, namely the Pediatric expansion of the phase 3 pivotal efficacy study of the Novavax recombinant spike protein vaccine with M Matrix adjuvant. The project's primary objectives are (1) to evaluate the efficacy of a 2-dose regimen of SARS-CoV-2 rS adjuvanted with Matrix-M1 compared to placebo against PCR-confirmed symptomatic COVID-19 illness diagnosed ≥ 7 days after completion of the second injection in the initial set of vaccinations of adolescent participants 12 to < 18 years of age; and (2) to describe the safety experience for the vaccine versus placebo in adolescent participants (12 to <18 years of age) based on solicited short-term reactogenicity by toxicity grade for 7 days following each vaccination (Days 0 and 21) after the initial set of vaccinations. Multiple additional objectives are also being evaluated. The design is a Phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants ≥ 18 years of age (Adult Main Study) with a Pediatric Expansion (This proposal is for the Pediatric Expansion). In the Pediatric Expansion, adolescent participants 12 to 17 years of age will be enrolled without stratification. Participants are followed for 2 years for safety, tolerability, efficacy, and immune responses. The expected sample size will be 3000 adolescents: 2000 will receive vaccine first and 1000 will receive placebo first. After 6 months, there will be a double-blind cross over. This study is expected to contribute the data necessary to allow for authorization of this vaccine in 12 to 17 year-olds in the US.