Statistical methods and sample size.
infection
VIRUS, INFECTION, SECONDARY
Across all 5 planned dose cohorts, 220 patients were planned for randomization. Approximately 60 patients were planned in a 1:1 ratio in cohort A to receive bemnifosbuvir or placebo. Each additional cohort was planned to enroll approximately 40 patients in a 3:1 ratio to receive bemnifosbuvir or placebo, respectively. As placebo data across cohorts were expected to be similar, analyses in cohorts B to E were planned to reuse placebo data from the preceding cohorts—hence the higher randomization ratio designed to minimize placebo enrollment into these cohorts. A sample size of 27 patients per arm was intended to ensure at least 80% power to detect a mean difference between treatment arms in change from baseline of viral RNA of between 0.7 and 1.1 logPrimary and secondary virologic outcomes were performed in the modified intent-to-treat infected (mITTI) population, defined as all randomized patients who received any amount of study drug and with at least 1 positive SARS-CoV-2 RT-PCR test at any time point during the study (regardless of the day of infection that the positive test occurred; testing was not conducted after day 7 of the study); patients were grouped according to the treatment assigned at randomization. The primary endpoint was evaluated in the bemnifosbuvir 550 mg arm versus the cohort A placebo arm and the bemnifosbuvir 1,100 mg arm versus a pooled placebo group consisting of patients from the placebo arms of both cohorts. Secondary analyses compared the bemnifosbuvir arm in each cohort with the pooled placebo group. Safety analyses were performed on the safety population, defined as all patients who received any amount of study drug; patients were grouped according to the treatment received.The primary endpoint was analyzed using analysis of covariance with baseline virus RNA as a covariate. Further statistical methods are provided in the File S1.