Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial

Abstract

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

Conflict of interest statement

C.H. and I.C. are scientists at Eiger BioPharmaceuticals, Inc., which provided the Interferon Lambda used for this study. J.G. serves on the board of Eiger BioPharmaceuticals, Inc. C.H. and I.C. own stock and options of Eiger BioPharmaceuticals, Inc. J.G. has an equity interest in Eiger BioPharmaceuticals, Inc. J.G. and I.C. are inventors on a pending patent application relating to the use of interferon lambda for coronavirus. Eiger BioPharmaceuticals played no role in study design, conduct of the study, or analysis of the data. All other authors declare no competing interests.

Figures

Fig. 1. CONSORT diagram.

Trial schematic showing participants screened, randomized, and followed through study completion.

Fig. 2. Kaplan–Meier analyses of the primary and key secondary outcome in the intention-to-treat population.

a Time until cessation of SARS-CoV-2 viral shedding from oropharyngeal swabs stratified by treatment arm, Lambda (blue) vs. placebo (red). b Time until resolution of all symptoms stratified by treatment arm, Lambda (blue) vs. placebo (red). In both panels, solid lines represent Kaplan–Meier survival probability; shading represents 95% confidence intervals. Source data available at https://purl.stanford.edu/hc972ys6733.

Fig. 3. Kaplan–Meier analyses of the primary outcome, stratified by baseline seropositivity and viral load.

a Time until cessation of SARS-CoV-2 viral shedding from oropharyngeal swabs stratified by baseline SARS-CoV-2 seropositivity, seropositive (dashed) and seronegative (solid), and treatment arm, Lambda (blue) vs. placebo (red). b Time until cessation of SARS-CoV-2 viral shedding from oropharyngeal swabs stratified by baseline SARS-CoV-2 oropharyngeal virus CT value, CT value ≥ 30 (dashed) and CT value < 30 (solid), and treatment arm, Lambda (blue) vs. placebo (red). In both panels, solid lines represent Kaplan–Meier survival probability; shading represents 95% confidence intervals. Source data available at https://purl.stanford.edu/hc972ys6733.