ACTIV-2: A Study for Outpatients With COVID-19

This is a master protocol to evaluate the safety and efficacy of multiple investigational agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly enhancing viral control in order to limit disease progression. The study includes both infused and non-infused agents and is a randomized controlled platform that allows agents to be added and dropped during the course of the study for efficient phase II and phase III testing of new agents within the same trial infrastructure. Version 7 of the protocol provided for blinded phase II evaluation of an investigational agent for superiority to placebo among participants at lower risk of progression to hospitalization or death, regardless of the mode of administration of the agent. Agents that graduate to phase III after initiation of the protocol version will be evaluated in persons at higher risk for progression to hospitalization or death for non-inferiority to an active comparator (monoclonal antibody cocktail of casirivimab plus imdevimab (REGEN-COV, Regeneron). This active comparator has been shown to be effective in this population in preventing hospitalization or death. When two or more agents are being evaluated in the same phase of the study, the trial design includes sharing of the control group (placebo in phase II and active comparator in phase III) for efficient evaluation of each agent. Investigational agents will be approved by the Trial Oversight Committee (TOC) for phase II evaluation based on the presence of in vitro data demonstrating promise as anti-SARS-CoV-2 therapeutics in pre-clinical testing, and for which there are suitable pharmacokinetics and safety data from phase I testing, or through clinical or research testing for a different indication, and agent availability. Investigational agents will be included in phase III evaluation based on agent entry criteria for phase III as outlined in the protocol (or by TOC approval based on data available outside ACTIV-2).