Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection

Andrew J. Muir, Mitchell L. Shiffman, Atif Zaman, Boris Yoffe, Andrew De La Torre, Steven Flamm, Stuart C. Gordon, Paul Marotta, John M. Vierling, Juan Carlos Lopez-Talavera, Kelly Byrnes-Blake, David Fontana, Jeremy Freeman, Todd Gray, Diana Hausman, Naomi N. Hunder, Eric Lawitz

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

Interferon lambda 1 (IFN-λ1) is a type III IFN that produces intracellular responses similar to those of IFN-α but in fewer cell types because of differences in the receptor distribution pattern, and this could potentially result in an improved safety profile. This was an open-label three-part study of patients with chronic hepatitis C virus (HCV) genotype 1 infection. Part 1 evaluated single-agent pegylated interferon lambda (PEG-IFN-λ) at 1.5 or 3.0 μg/kg administered every 2 weeks or weekly for 4 weeks in patients who had relapsed after previous IFN-α-based treatment. Part 2 evaluated weekly doses of PEG-IFN-λ ranging from 0.5 to 2.25 μg/kg in combination with ribavirin (RBV) for 4 weeks in treatment-relapse patients. Part 3 evaluated weekly PEG-IFN-λ at 1.5 μg/kg in combination with RBV for 4 weeks in treatment-naive patients. Fifty-six patients were enrolled: 24 patients in part 1, 25 patients in part 2, and 7 patients in part 3. Antiviral activity was observed at all PEG-IFN-λ dose levels (from 0.5 to 3.0 μg/kg). Two of seven treatment-naive patients (29%) achieved rapid virological response. Treatment was well tolerated with minimal flu-like symptoms and no significant hematologic changes other than RBV-associated decreases in hemoglobin. The most common adverse events were fatigue (29%), nausea (12%), and myalgia (11%). Six patients experienced increases in aminotransferases that met protocol-defined criteria for dose-limiting toxicity (DLT) or temporarily holding therapy with PEG-IFN-λ. Most DLT occurred in patients with high PEG-IFN-λ exposure. Conclusion: Weekly PEG-IFN-λ with or without daily RBV for 4 weeks is well tolerated with minimal adverse events and hematologic effects and is associated with clear antiviral activity across a broad range of doses in patients with chronic HCV. (HEPATOLOGY 2010;52:822-832)

Original languageEnglish (US)
Pages (from-to)822-832
Number of pages11
JournalHepatology
Volume52
Issue number3
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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    Muir, A. J., Shiffman, M. L., Zaman, A., Yoffe, B., De La Torre, A., Flamm, S., Gordon, S. C., Marotta, P., Vierling, J. M., Lopez-Talavera, J. C., Byrnes-Blake, K., Fontana, D., Freeman, J., Gray, T., Hausman, D., Hunder, N. N., & Lawitz, E. (2010). Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology, 52(3), 822-832. https://doi.org/10.1002/hep.23743