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

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Hepatology. 2010 May 14. [Epub ahead of print]

Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in

patients with chronic genotype 1 hepatitis C virus infection.

Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S, Gordon SC,

Marotta P, Vierling JM, -Talavera J, Byrnes-Blake K, Fontana D,

Freeman J, Gray T, Hausman D, Hunder NN, Lawitz E.

Division of Gastroenterology, Duke University, Durham, NC.

Abstract

Interferon lambda 1 (IFN-lambda1) is a type III IFN that produces intracellular

responses similar to those of IFN-alpha 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-lambda) at 1.5 or

3.0 mug/kg administered every 2 weeks or weekly for 4 weeks in patients who had

relapsed after previous IFN-alpha-based treatment. Part 2 evaluated weekly doses

of PEG-IFN-lambda ranging from 0.5 to 2.25 mug/kg in combination with ribavirin

(RBV) for 4 weeks in treatment-relapse patients. Part 3 evaluated weekly

PEG-IFN-lambda at 1.5 mug/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-lambda dose levels (from 0.5 to 3.0 mug/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-lambda. Most DLT occurred in patients with high PEG-IFN-lambda exposure.

Conclusion: Weekly PEG-IFN-lambda 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;).

PMID: 20564352 [PubMed - as supplied by publisher]

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