In three substudies, three therapeutic agents will be evaluated as an add-on therapy to SoC.
These agents are:
Participants will be randomly assigned to receive either SoC plus one of the test agents or SoC plus placebo. Randomization will proceed in two stages. At the first stage, each participant will be assigned to one of the sub-studies with equal probability. At the second stage, each participant will be assigned to either the test agent or its matching placebo in an n:1 ratio, where n = the number of substudies currently active in the master protocol and for which the patient is eligible to receive. With three agents and SoC, for example, this procedure results in a randomization ratio of 1:1:1:1 if the patient is eligible to receive all three agents.
Inclusion of a placebo for each agent enables masking of study participants and clinical personnel to treatment assignment at the second stage. Data from patients receiving SoC plus placebo will be pooled across agents for comparative analyses and hypothesis testing.
If there are supply limitations on any product, the sub-study containing that product, or its matching placebo will be temporarily closed to enrollment.
The initial SoC will be remdesivir, based on the results of the ACTT-1 study. Participants will receive SoC as follows:
Duration of SoC therapy: