A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics

[Guest guest]

Journal of Hepatology

Volume 44, Issue 4 , April 2006, Pages 671-678

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

G. Baina, , , D. Kaitab, M. Yoshidac, Mark G. Swaind, E.

Heathcotee, Avidan U. Neumannf, Michele Fiscellag, Ren Yug, Blaire L.

Osborng, W. Croning, W. Freimuthg, G. McHutchisonh and

G. Mani Subramaniang

aUniversity of Alberta, Liver Unit, Zeidler Ledcor Center, 130 University

Campus, Edmonton, Alberta, Canada, T6G 2X8

bUniversity of Manitoba, Winnipeg, Canada

cUniversity of British Columbia, Vancouver, Canada

dUniversity of Calgary, Calgary, Canada

eUniversity of Toronto, Toronto, Canada

fBar-Illan University, Ramat-Gan, Israel

gHuman Genome Sciences, Inc., Rockville, MD, USA

hDuke Clinical Research Institute, and Division of Gastroenterology, Duke

University, Durham, NC, USA

Received 14 November 2005; revised 14 December 2005; accepted 16 December

2005. Available online 30 January 2006.

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 & #956;g.

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 & #956;g. 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.

Keywords: Albumin-interferon alfa; Chronic hepatitis C; Genotype 1;

Pharmacokinetics; Viral kinetics

The authors who have taken part in this study have declared a relationship

with the manufacturers of the drugs involved and they received funding from

the drug companies involved to carry out their research.

Corresponding author. Tel.: +1 708 492 8128.

_________________________________________________________________

Don’t just search. Find. Check out the new MSN Search!

http://search.msn.click-url.com/go/onm00200636ave/direct/01/