A Phase 3, multicenter, randomized, double-blind, 24-week study of the clinical and antiviral effect of S-217622 compared with placebo in non-hospitalized participants with COVID-19

DESIGN ACTIV-2d/A5407 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic non-hospitalized adults with high and low risk of progression to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. REGIMEN S-217622 or placebo orally once daily for 5 days (375 mg on Day 1 followed by 125 mg on Days 2 to 5).DURATION Days 1 through 29 intensive study, followed by limited study through 24 weeks. STRATIFICATION Randomization will be stratified by geographic region and high risk versus (vs.) low risk of severe coronavirus disease 2019 (COVID-19)POPULATION Outpatient adults (≥18 years) with: a) documented positive SARS-CoV-2 nucleic acid or antigen test from a sample collected ≤120 hours (5 days) prior to randomization, b) onset of symptoms of COVID-19 ≤5 days prior to randomization, c) presence of 1 or more select COVID-19 symptoms within 24 hours prior to randomization. Participants will be eligible regardless of vaccination status and will be classified as either high risk or low risk. High-risk participants: defined as aged ≥65 years or those with presence of high-risk conditions.Low-risk participants: defined as those not meeting the high-risk definition. SAMPLE SIZE Approximately 1490 participants (745 on S-217622 and 745 on placebo) will be randomized into the study. Approximately 50% of enrollment will be high-risk participants and 50% will be low-risk participants. All locally provided standard-of-care, including COVID-19 monoclonal antibody (mAb) treatment, outpatient intravenous (IV) remdesivir, and oral antivirals compatible with S-217622 will be permitted after enrollment, in addition to the randomized treatment.OUTCOME MEASURES The primary outcome measure is: Time in days from the start of S-217622 to sustained symptom resolution.