CoVPN 3502 / ACTIV-2/A5401

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Abstract A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2 (CoVPN 3502) Transmission of SARS-CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020). Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection from household contacts develop symptoms of COVID-19 (Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b). Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic disease. Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of time between symptomatic infection in the source individual and the development of symptoms in newly infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020) (Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. Given the speed at which this outbreak has spread and how it has impacted almost every community globally, there is an urgent need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with symptomatic disease. This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure to individuals with SARS-CoV-2 infection. ACTIV-2/A5401: Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt Out COVID) – Brii Biosciences Agent Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19. It begins with a phase II evaluation, followed by a transition into a larger phase III evaluation for promising agents. This supplement represents activity for the Brii Biosciences Agent. The trial is a randomized, blinded, controlled adaptive platform that allows agents to be added and dropped during the course of the study for efficient testing of new agents against placebo within the same trial infrastructure. When two or more new agents are being tested concurrently, the same placebo will be used, if feasible. The primary outcome measures in the phase II evaluation will be duration of symptoms, similar to the outcome used for outpatient influenza studies, loss of detection of SARS-CoV-2 RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a phase II agent will continue to be evaluated in phase III will be made after the last participant randomized to that agent or placebo group completes their day 28 phase II visit. If continued, data collected from participants enrolled in phase II will be included in the phase III evaluation. The phase III evaluation is a continuation of the phase II trial for agents that meet study-defined criteria for further evaluation and for which sufficient investigational agent is available. An agent may also enter directly into phase III evaluation based on Trial Oversight Committee (TOC) assessments. The fully powered phase III trial will evaluate the efficacy of each selected investigational agent compared to placebo to prevent hospitalization and death in non-hospitalized adults with COVID-19. The protocol will be amended when information becomes available from within or outside of the trial indicating that further randomization to a placebo is inappropriate.