PROJECT SUMMARY/ABSTRACT The ACTIV public-private partnership has prioritized, designed, and harmonized five adaptive master protocols for ACTIV clinical trials, and selected numerous NIH-supported networks to launch these clinical trials to test prioritized therapeutic candidates. Master protocols allow coordinated and efficient evaluation of multiple investigational agents as they become available, but within the same clinical trial structure, across multiple study sites. Adaptive protocols swiftly weed out experimental drugs that do not demonstrate effectiveness and identify those that do. Adaptive master protocols reduce administrative burden and cost, provide a flexible framework to rapidly identify drugs that work, and rapidly move additional experimental agents into the trial. The ACTIV-1 master protocol is evaluating the safety and efficacy of at least three immune modulators (initially infliximab, abatacept and cencicrivoroc when given as an add-on therapy to standard of care, which currently includes remdesivir, The different treatments will be assessed with respect to illness severity, recovery speed, mortality and hospital resource utilization. Dr. Powderly is the Principal investigator for ACTIV-1 and the purpose of this supplement is to provide funding support for him and his Administrative Coordinator. In his role, he will participate in regular conference calls with ACTIV and NCATS leadership as well as leading weekly protocol team calls and regular calls with local PIs. He will review all safety events and other study end-points and present regular reports to the DSMB. He will also coordinate the reporting of the results and the writing of study manuscripts.

PROJECT NARRATIVE The ACTIV-1 master protocol is evaluating the safety and efficacy of at least three immune modulators (initially infliximab, abatacept and cencicrivoroc when given as an add-on therapy to standard of care, that includes remdesivir, The different treatments will be assessed with respect to illness severity, recovery speed, mortality and hospital resource utilization. Dr. Powderly is the Principal investigator for ACTIV 1.