Trial Design and Oversight
Tixagevimab-cilgavimab
DISEASE PROGRESSION
ACTIV-2/A5401 is a multicenter, controlled platform randomized clinical trial designed to evaluate investigational agents for treatment of nonhospitalized adults with mild-to-moderate COVID-19. The trial protocol is provided in Tixagevimab-cilgavimab administered IV and IM were studied as separate agents, and each group was enrolled in parallel and compared with placebo. Participants were randomized in 2 steps to an investigational agent group (eg, IM tixagevimab-cilgavimab, IV tixagevimab-cilgavimab, or another agent in the platform), and then to blinded active agent or placebo for that agent, within the assigned group. For each investigational agent, a control arm was constructed by pooling all participants who were eligible for that agent group and randomized to placebo for that agent or any other concurrently enrolling agent. Randomization was stratified by time from symptom onset (≤5 or >5 days) and risk of disease progression (lower or higher). Details on trial design, including randomization scheme, are given in eMethods 1 in Each phase 2 evaluation was powered on the primary virologic outcome. The target sample size for each phase 2 evaluation was 220 (110 each for active agent and placebo), affording at least 82% power to detect a 20% absolute increase in proportion with viral RNA below the lower limit of quantification vs placebo, with 2-sided 5% type I error.