This adaptive, randomized, placebo-controlled platform study is designed to rapidly assess multiple candidate agents as treatments for COVID-19 in hospitalized patients. Candidate agents will be evaluated frequently (through ongoing monitoring) for futility and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.~For inclusion, participants will need to be hospitalized with a clinical status of Grade 2 to Grade 5, as defined by the following Clinical Severity Status 8-Point Ordinal Scale:~Death~Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities~Participants will be randomized equally to either the candidate agent plus standard of care (SoC) or placebo plus SoC in a double-blind fashion. Participants who are randomized to placebo plus SoC will subsequently be randomized equally to a matching placebo corresponding to an available agent whose sub-protocol the patient qualified for (ie, a 2-stage randomization). Each participant in the placebo plus SoC group will only receive one type of placebo. Randomization will be stratified by baseline clinical severity of 2 on the 8-point ordinal scale (yes/no) and remdesivir use at baseline (yes/no).~The study will evaluate each candidate agent separately as an add-on to the SoC to assess safety and efficacy. The comparator group for a candidate agent will include participants randomized to the placebo arm of any sub-protocol according to the following conditions:~Apremilast sub-protocol: participants who were enrolled concurrently to apremilast and who would have been eligible for the apremilast sub-protocol.~Lanadelumab sub-protocol: at a site where at least one participant was randomized to either lanadelumab active or placebo arms.~Zilucoplan sub-protocol: at a site where at least one participant was randomized to either the zilucoplan active or placebo arms.
The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.