Safety and Antiviral Activity of Albinterferon Alfa-2b in Prior Interferon Nonresponders With Chronic Hepatitis C

published online 11 November 2008.

Background & Aims

Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens.

Methods

A total of 115 patients were assigned to 5 groups given 1200 μg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 μg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks.

Results

The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-μg group.

Conclusions

In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.

Abbreviations used in this paper: AEs, adverse events, alb-IFN, albinterferon alfa-2b, ANC, absolute neutrophil count, CES-D, Center for Epidemiologic Studies Depression scale, CHC, chronic hepatitis C, Gt, genotype, HCV, hepatitis C virus, LOD, limit of detection, PEG-IFN, pegylated interferon, RBV, ribavirin, SVR, sustained virologic response

⁎ University of Florida, Gainesville, Florida

‡ Metropolitan Research, Fairfax, Virginia

§ Mayo Clinic, Scottsdale, Arizona

∥ Johns Hopkins University, Baltimore, Maryland

¶ Baylor University Medical Center, Dallas, Texas

# Duke University, Durham, North Carolina

⁎⁎ University of Florida, Jacksonville, Florida

‡‡ Mayo Clinic, Jacksonville, Florida

§§ Mayo Clinic, Rochester, Minnesota

¶¶ Duke Clinical Research Institute, Durham, North Carolina

∥∥ Human Genome Sciences, Inc, Rockville, Maryland

Address requests for reprints to: David R. Nelson, MD, Professor of Medicine, Director of Hepatology and Liver Transplantation, University of Florida College of Medicine, Box 100214, Room M-440, Gainesville, Florida 32610-0214. fax: (352) 392-7393

The conduct of the study was coordinated centrally by the Duke Clinical Research Institute, Durham, North Carolina. The investigators had full access to the data.

The authors disclose the following: Supported by Human Genome Sciences, Inc., Rockville, MD, and Novartis Pharma AG, Basel, Switzerland. David R. Nelson, Vinod Rustgi, Vijayan Balan, Mark S. Sulkowski, Gary L. Davis, Andrew J. Muir, Louis R. Lambiase, Rolland C. Dickson, Russell H. Weisner, and John G. McHutchison have received research support from Human Genome Sciences. Michele Fiscella, Patrick W. Cronin, Erik Pulkstenis, and G. Mani Subramanian are employees of Human Genome Sciences.

PII: S1542-3565(08)01121-X

doi:10.1016/j.cgh.2008.10.035

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