Change in SARS-CoV-2 neutralizing antibody levels.Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death.Composite of cardiovascular events and thromboembolic events.Composite of death or serious clinical COVID-19 related events.Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.Įxtrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The international trials within this protocol will be conducted in several hundred clinical sites. Participants will be followed for 18 months following randomization. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm or futility for the investigational agent. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.īoth ordinal outcomes are used to assess futility because it is currently unclear whether the investigational agents under study will primarily influence non-pulmonary outcomes, for which risk is increased with SARS-CoV-2 infection, in part, through mechanisms that may be different from those that influence pulmonary outcomes.įor investigational agents passing this futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings.
This will continue until approximately 300 participants are enrolled and followed for 5 days. For the study of each agent, at the outset of the trial, only participants in disease severity stratum 1 will be enrolled. For investigational drugs with minimal pre-existing safety knowledge, the pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).Īn independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. Randomization will be stratified by study site pharmacy and disease severity.
When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo. This allows for efficient testing of new drugs against placebo and standard of care (SOC) treatment within the same study. The protocol is for a randomized, blinded, controlled platform study that allows investigational drugs to be added and dropped during the course of the study.
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. Why Should I Register and Submit Results?.
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