ABSTRACT
Background: We assessed the efficacy of a single dose of peginterferon lambda in preventing clinical events among acutely symptomatic COVID-19 outpatients. Method(s): We conducted a placebo-controlled, randomized, adaptive platform trial among predominantly vaccinated SARS-CoV-2-positive adults in Brazil and Canada receiving either one subcutaneous injection of peginterferon lambda or placebo. The primary composite endpoint was medical admission to hospital, defined as either observation in a COVID-19 emergency setting for > 6 hours, or transfer to a tertiary hospital due to symptomatic COVID-19 within 28 days post-randomization. Result(s): For this evaluation, 931 patients received peginterferon lambda and 1018 received placebo. 84% of the population were vaccinated and the trial occurred across multiple COVID-19 variants. In the primary analysis of patients, the primary outcome was reduced by 51% in the peginterferon lambda vs. placebo groups (relative risk 0.49 [25/916 vs 57/1003], 95% Bayesian credible interval 0.30-0.76, posterior probability >99.9%). This effect was maintained in subgroup analyses including COVID-19-related hospitalization alone (relative risk 0.57, 95% Bayesian credible intervals 0.33-0.95, ) and COVID-19-related hospitalization or death (Hazard ratio 0.59, 95% Bayesian credible interval 0.35- 0.97). The effects were consistent across dominant variants and vaccination status. Among individuals with a high viral level at baseline, peginterferon lambda resulted in lower viral loads by Day 7, compared to placebo. The incidence of adverse events was similar in the two groups. Conclusion(s): Among predominantly vaccinated outpatients with COVID-19, single-dose of peginterferon lambda resulted in significantly decreased clinical events.