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

J Hepatol. 2006 Apr;44(4):671-8. doi: 10.1016/j.jhep.2005.12.011. Epub 2006 Jan 30.

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 1,200 microg.

Results: A 2 log(10) 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 1,200 microg. The mean HCV RNA reduction at Week 4 in these two higher-dose cohorts was 3.2 log(10) 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Arthralgia / chemically induced
  • Chills / chemically induced
  • Dose-Response Relationship, Drug
  • Drug Tolerance
  • Fatigue / chemically induced
  • Female
  • Genotype
  • Half-Life
  • Headache / chemically induced
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / virology
  • Humans
  • Injections, Subcutaneous
  • Interferon-alpha* / administration & dosage
  • Interferon-alpha* / adverse effects
  • Interferon-alpha* / pharmacokinetics
  • Male
  • Middle Aged
  • RNA, Viral / analysis
  • Recombinant Proteins* / administration & dosage
  • Recombinant Proteins* / adverse effects
  • Recombinant Proteins* / pharmacokinetics
  • Serum Albumin* / administration & dosage
  • Serum Albumin* / adverse effects
  • Serum Albumin* / pharmacokinetics
  • Serum Albumin, Human

Substances

  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Serum Albumin
  • albuferon
  • Serum Albumin, Human