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.
OBJECTIVE
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.
University of Alberta, Liver Unit, Zeidler Ledcor Center, 130 University Campus, Edmonton, Alberta, Canada, T6G 2X8. vince.bain@ualberta.ca
Vincent G
VG
Bain
Kelly D
KD
Kaita
Eric M
EM
Yoshida
Mark G
MG
Swain
E Jenny
EJ
Heathcote
Avidan U
AU
Neumann
Michele
M
Fiscella
Ren
R
Yu
Blaire L
BL
Osborn
Patrick W
PW
Cronin
William W
WW
Freimuth
John G
JG
McHutchison
G Mani
GM
Subramanian
D000328:Adult; D018771:Arthralgia / Q000139:chemically induced; D023341:Chills / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005838:Genotype; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000075462:Serum Albumin, Human
D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012709:Serum Albumin; C473631:albuferon; D000075462:Serum Albumin, Human