TY - JOUR
T1 - 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
AU - Bain, Vincent G.
AU - Kaita, Kelly D.
AU - Yoshida, Eric M.
AU - Swain, Mark G.
AU - Heathcote, E. Jenny
AU - Neumann, Avidan U.
AU - Fiscella, Michele
AU - Yu, Ren
AU - Osborn, Blaire L.
AU - Cronin, Patrick W.
AU - Freimuth, William W.
AU - McHutchison, John G.
AU - Subramanian, G. Mani
PY - 2006/4/1
Y1 - 2006/4/1
N2 - 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.
AB - 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.
KW - Albumin-interferon alfa
KW - Chronic hepatitis C
KW - Genotype 1
KW - Pharmacokinetics
KW - Viral kinetics
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U2 - 10.1016/j.jhep.2005.12.011
DO - 10.1016/j.jhep.2005.12.011
M3 - Article
C2 - 16487617
AN - SCOPUS:33644918919
SN - 0168-8278
VL - 44
SP - 671
EP - 678
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -