A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients

Vincent G. Bain, Kelly D. Kaita, Eric M. Yoshida, Mark G. Swain, E. Jenny Heathcote, Avidan U. Neumann, Michele Fiscella, Ren Yu, Blaire L. Osborn, Patrick W. Cronin, William W. Freimuth, John G. McHutchison, G. Mani Subramanian

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: Recombinant human albumin-interferon alfa (alb-IFN) is a novel 85.7-kD recombinant protein consisting of interferon alfa-2b genetically fused to human serum albumin. Methods: A phase 2, open-label, dose-ranging study was conducted in IFN-alfa-naïve patients with genotype 1 chronic hepatitis C to evaluate the antiviral activity, safety, and pharmacokinetics of alb-IFN. Fifty-six patients were enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts of 200, 450, 670, 900, and 1200 μg. Results: A 2 log10 IU/mL or greater reduction in hepatitis C virus (HCV) RNA at Week 4 was observed in 69% (18/26) of patients who received the higher alb-IFN doses of 900 and 1200 μg. The mean HCV RNA reduction at Week 4 in these two higher-dose cohorts was 3.2 log10 IU/mL. Modeling of viral kinetics demonstrated a biphasic response that was dose dependent. Adverse events were mostly mild to moderate in severity. The most common adverse events were headache (73%), chills (63%), fatigue (61%), and arthralgia (55%). The median terminal half-life was 141 h consistent with previous alb-IFN data from IFN-alfa-experienced patients. Conclusions: Alb-IFN demonstrated significant antiviral activity and was well tolerated in patients with HCV genotype 1 infection.

Original languageEnglish (US)
Pages (from-to)671-678
Number of pages8
JournalJournal of Hepatology
Volume44
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Albumin-interferon alfa
  • Chronic hepatitis C
  • Genotype 1
  • Pharmacokinetics
  • Viral kinetics

ASJC Scopus subject areas

  • Hepatology

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