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

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;)