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

193 Citations (Scopus)

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 2010

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Ribavirin
Virus Diseases
Hepacivirus
Interferons
Genotype
Chronic Hepatitis C
Antiviral Agents
Therapeutics
Myalgia
Transaminases
Nausea
Fatigue
Hemoglobins

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. / Muir, Andrew J.; Shiffman, Mitchell L.; Zaman, Atif; Yoffe, Boris; De La Torre, Andrew; Flamm, Steven; Gordon, Stuart C.; Marotta, Paul; Vierling, John M.; Lopez-Talavera, Juan Carlos; Byrnes-Blake, Kelly; Fontana, David; Freeman, Jeremy; Gray, Todd; Hausman, Diana; Hunder, Naomi N.; Lawitz, Eric.

In: Hepatology, Vol. 52, No. 3, 09.2010, p. 822-832.

Research output: Contribution to journalArticle

Muir, AJ, Shiffman, ML, Zaman, A, Yoffe, B, De La Torre, A, Flamm, S, Gordon, SC, Marotta, P, Vierling, JM, Lopez-Talavera, JC, Byrnes-Blake, K, Fontana, D, Freeman, J, Gray, T, Hausman, D, Hunder, NN & 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, vol. 52, no. 3, pp. 822-832. https://doi.org/10.1002/hep.23743
Muir, Andrew J. ; Shiffman, Mitchell L. ; Zaman, Atif ; Yoffe, Boris ; De La Torre, Andrew ; Flamm, Steven ; Gordon, Stuart C. ; Marotta, Paul ; Vierling, John M. ; Lopez-Talavera, Juan Carlos ; Byrnes-Blake, Kelly ; Fontana, David ; Freeman, Jeremy ; Gray, Todd ; Hausman, Diana ; Hunder, Naomi N. ; Lawitz, Eric. / Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. In: Hepatology. 2010 ; Vol. 52, No. 3. pp. 822-832.
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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)",
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AU - Yoffe, Boris

AU - De La Torre, Andrew

AU - Flamm, Steven

AU - Gordon, Stuart C.

AU - Marotta, Paul

AU - Vierling, John M.

AU - Lopez-Talavera, Juan Carlos

AU - Byrnes-Blake, Kelly

AU - Fontana, David

AU - Freeman, Jeremy

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