Randomized Controlled Trial

. 2021 Mar 30;12(1):1967.

doi: 10.1038/s41467-021-22177-1.

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

Prasanna Jagannathan^{1

2}, Jason R Andrews^#³, Hector Bonilla^#³, Haley Hedlin^#⁴, Karen B Jacobson³, Vidhya Balasubramanian⁴, Natasha Purington⁴, Savita Kamble⁵, Christiaan R de Vries³, Orlando Quintero³, Kent Feng⁵, Catherine Ley³, Dean Winslow³, Jennifer Newberry⁶, Karlie Edwards³, Colin Hislop⁷, Ingrid Choong⁷, Yvonne Maldonado⁸, Jeffrey Glenn^{3

9}, Ami Bhatt^{3

10}, Catherine Blish³, Taia Wang^{3

9}, Chaitan Khosla¹¹, Benjamin A Pinsky^{3

12}, Manisha Desai⁴, Julie Parsonnet³, Upinder Singh^{13

14}

Affiliations

¹ Department of Medicine, Stanford University, Stanford, CA, USA. prasj@stanford.edu.
² Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. prasj@stanford.edu.
³ Department of Medicine, Stanford University, Stanford, CA, USA.
⁴ Quantitative Sciences Unit, Stanford University, Stanford, CA, USA.
⁵ Stanford Center for Clinical Research, Stanford University, Stanford, CA, USA.
⁶ Department of Emergency Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Pediatrics, Stanford University, Stanford, CA, USA.
⁸ Eiger BioPharmaceuticals, Palo Alto, CA, USA.
⁹ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹⁰ Department of Genetics, Stanford University, Stanford, CA, USA.
¹¹ ChEM-H, Stanford University, Stanford, CA, USA.
¹² Department of Pathology, Stanford University, Stanford, CA, USA.
¹³ Department of Medicine, Stanford University, Stanford, CA, USA. usingh@stanford.edu.
¹⁴ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. usingh@stanford.edu.

^# Contributed equally.

PMID: 33785743
PMCID: PMC8009873
DOI: 10.1038/s41467-021-22177-1

Randomized Controlled Trial

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

Prasanna Jagannathan et al. Nat Commun. 2021.

. 2021 Mar 30;12(1):1967.

doi: 10.1038/s41467-021-22177-1.

Authors

Affiliations

¹ Department of Medicine, Stanford University, Stanford, CA, USA. prasj@stanford.edu.
² Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. prasj@stanford.edu.
³ Department of Medicine, Stanford University, Stanford, CA, USA.
⁴ Quantitative Sciences Unit, Stanford University, Stanford, CA, USA.
⁵ Stanford Center for Clinical Research, Stanford University, Stanford, CA, USA.
⁶ Department of Emergency Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Pediatrics, Stanford University, Stanford, CA, USA.
⁸ Eiger BioPharmaceuticals, Palo Alto, CA, USA.
⁹ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹⁰ Department of Genetics, Stanford University, Stanford, CA, USA.
¹¹ ChEM-H, Stanford University, Stanford, CA, USA.
¹² Department of Pathology, Stanford University, Stanford, CA, USA.
¹³ Department of Medicine, Stanford University, Stanford, CA, USA. usingh@stanford.edu.
¹⁴ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. usingh@stanford.edu.

^# Contributed equally.

PMID: 33785743
PMCID: PMC8009873
DOI: 10.1038/s41467-021-22177-1

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.

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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.

See this image and copyright information in PMC

References

1. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) (Johns Hopkins University, 2021). https://coronavirus.jhu.edu/map.html.
1. Baud D, et al. Real estimates of mortality following COVID-19 infection. Lancet Infect. Dis. 2020;20:773. doi: 10.1016/S1473-3099(20)30195-X. - DOI - PMC - PubMed
1. Park A, Iwasaki A. Type I and Type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27:870–878. doi: 10.1016/j.chom.2020.05.008. - DOI - PMC - PubMed
1. Kotenko SV. IFN-lambdas. Curr. Opin. Immunol. 2011;23:583–590. doi: 10.1016/j.coi.2011.07.007. - DOI - PMC - PubMed
1. Zhou Z, et al. Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J. Virol. 2007;81:7749–7758. doi: 10.1128/JVI.02438-06. - DOI - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Associated data

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LinkOut - more resources

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