A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. Remdesivir (GS-5734) is a broad-spectrum nucleotide prodrug that inhibits RNA-dependent RNA polymerase activity among a diverse group of RNA viruses including filoviruses, paramyxoviruses and pathogenic coronaviruses. Nonclinical in vitro and in vivo data suggests that remdesivir might be useful for the treatment of COVID-19 for which no medical countermeasures are currently approved and support testing the efficacy of remdesivir treatment among hospitalized adults with COVID-19. This study is an adaptive, randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized 394 adult patients diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to 50 sites globally. All subjects will undergo a series of efficacy, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will be obtained on Day 1; 3, 5, 8, 11; and Day 15 and 29. The proposed primary outcome, a 7-point ordinal scale at Day 15, will be defined based on blinded review of data from the first 100 subjects. This study utilizes an adaptive design that maximizes our efficiency in identifying a safe and efficacious therapeutic agent for COVID-19 during the current outbreak. As the a multicenter, multinational randomized controlled study, we will be able to acquire rigorous data about the safety and efficacy of investigational therapeutic agents for COVID-19 that will lead to generalizable evidence. Last, collecting clinical and virologic data using a standardized timeline and collection instruments should provide valuable information about the clinical course of and morbidities associated with severe COVID-19 in a diverse group of hospitalized adult patients.