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.

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.

• Authors: 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
• Journal: Journal of hepatology (J Hepatol) Vol. 44 Issue 4 Pg. 671-8 (Apr 2006) ISSN: 0168-8278 [Print] Netherlands
• PMID: 16487617 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

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

Topics

• 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, genetics, virology)
• Humans
• Injections, Subcutaneous
• Interferon-alpha (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Middle Aged
• RNA, Viral (analysis)
• Recombinant Proteins (administration & dosage, adverse effects, pharmacokinetics)
• Serum Albumin (administration & dosage, adverse effects, pharmacokinetics)
• Serum Albumin, Human