A study to evaluate the efficacy and safety of Bemnifosbuvir in High-Risk Outpatients with COVID-19

INTERVENTION: Product Name: Bemnifosbuvir Hemisulfate Product Code: BEM; AT‐527 Pharmaceutical Form: Tablet INN or Proposed INN: Bemnifosbuvir CAS Number: 2241337‐84‐6 Current Sponsor code: AT‐527 Other descriptive name: AT‐511 ‐ hemisulfate salt, RO7496998 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 275‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: COVID‐19 ; MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID‐19 System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of BEM compared with placebo in reducing all‐cause hospitalization or all‐cause death in COVID‐19 outpatients receiving only supportive care. Primary end point(s): The primary efficacy endpoint is the proportion of subjects in the supportive‐care‐only population who are hospitalized for any cause or died due to any cause through Day 29 Secondary Objective: • To evaluate the efficacy of BEM compared with placebo on:; ‐ COVID‐19 related hospitalization or all‐cause death through Day 29; ‐ All‐cause death through Day 29 and Day 60; ‐ COVID‐19‐related complications (e.g., death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, cardiac failure); ‐ COVID‐19‐related medically attended visits (hospitalization, emergency room (ER) visit, urgent care visit, physician’s office visit, or telemedicine visit) or all‐cause death through Day 29 and Day 60; ‐COVID‐19 symptom relapse; • To evaluate the antiviral activity of BEM compared with placebo on viral load rebound; • To evaluate the safety of BEM compared with placebo; Timepoint(s) of evaluation of this end point: Through Day 29 SECONDARY OUTCOME: Secondary end point(s): • Proportion of subjects in the supportive‐care‐only population with COVID‐19‐related hospitalization or who died due to any cause through Day 29; • Proportion of subjects in the overall study population, the supportive‐care‐only population, and the combination antiviral population who died due to any cause through Day 29 and Day 60; • Proportion of subjects in the supportive‐care‐only population with COVID‐19‐related complications (e.g., death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, cardiac failure); • Proportion of subjects in the supportive‐care‐only population with COVID‐19‐related medically attended visits (hospitalization, emergency room (ER) visit, urgent care visit, physician’s office visit, or telemedicine visit) or who died due to any cause through Day 29 and Day 60; • Proportion of subjects with COVID‐19 symptom relapse in each population through Day 29 ; • Proportion of subjects in each population with viral load rebound through Day 29 ; Timepoint(s) of evaluation of this end point: Various timepoints as described, primarily through day 29 and up to day 60; INCLUSION CRITERIA: 1. Willing and able to provide informed consent. 2. Positive SARS‐CoV‐2 diagnostic test (RT‐PCR or validated rapid antigen test) conducted = 5 days prior to randomization. Note: The test may be obtained locally. A documented historical record of positive result (RT‐PCR or validated rapid antigen test) from test conducted = 5 days prior to randomization is acceptable. 3. Mild or moderate COVID‐19 with symptom onset = 5 days before randomization and at least one COVID‐19 related symptom present at time of screening: • Mild COVID‐19: ‐ Symptoms of mild illness with COVID‐19, which could include fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, and loss of taste or smell, without shortness of breath or dyspnea ‐ No clinical signs indicative of moderate, severe, or critical illness severity • Moderate COVID‐19: ‐ Symptoms of moderate illness with COVID‐19, which could include any symptom of mild