Peginterferon-lambda for the treatment of COVID-19 in outpatients

Feld, J. J.; Kandel, C.; Biondi, M. J.; Kozak, R. A.; Zahoor, M. A.; Lemieux, C.; Borgia, S. M.; Boggild, A. K.; Powis, J.; McCready, J.; Tan, D. H.; Chan, T.; Coburn, B.; Kumar, D.; Humar, A.; Chan, A.; O'Neil, B.; Noureldin, S.; Booth, J.; Hong, R.; Smookler, D.; Aleyadeh, W.; Patel, A.; Barber, B.; Casey, J.; Hiebert, R.; Mistry, H.; Choong, I.; Hislop, C.; Santer, D.; Tyrrell, D. L.; Glenn, J. S.; Gehring, A. J.; Janssen, H. L.; Hansen, B.

Background: There are currently no effective treatments for outpatients with coronavirus disease 2019 (COVID-19). Interferon-lambda-1 is a Type III interferon involved in the innate antiviral response with activity against respiratory pathogens. Methods: In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomized to a single subcutaneous injection of peginterferon-lambda 180mcg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. The primary endpoint was proportion negative for SARS-CoV-2 RNA on Day 7 post-injection. Findings: There were 30 patients per arm, with median baseline SARS-CoV-2 viral load of 6.71 (IQR 1.3-8.0) log copies/mL. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon-lambda than placebo (p=0.04). On Day 7, 24 participants (80%) in the peginterferon-lambda group had an undetectable viral load compared to 19 (63%) in the placebo arm (p=0.15). After controlling for baseline viral load, peginterferon lambda treatment resulted in a 4.12-fold (95CI 1.15-16.7, p=0.029) higher likelihood of viral clearance by Day 7. Of those with baseline viral load above 10E6 copies/mL, 15/19 (79%) in the peginterferon-lambda group were undetectable on Day 7 compared to 6/16 (38%) in the placebo group (p=0.012). Adverse events were similar between groups with only mild reversible transaminase elevations more frequently observed in the peginterferon-lambda group. Interpretation: Peginterferon-lambda accelerated viral decline in outpatients with COVID-19 resulting in a greater proportion with viral clearance by Day 7, particularly in those with high baseline viral load. Peginterferon-lambda may have potential to prevent clinical deterioration and shorten duration of viral shedding. (NCT04354259)