Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C.
The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFNalpha)-2a 180 microg one time per week (qwk), or alb-IFN 900 or 1,200 microg once every two weeks (q2wk), or 1,200 microg once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 microg q2wk, 55.5% (61/110) with 1,200 microg q2wk, and 50.9% (59/116) with 1,200 microg q4wk, and 57.9% (66/114) with PEG-IFNalpha-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 microg q2wk, 18.2% with 1,200 microg q2wk and 12.1% with 1,200 microg q4wk, and 6.1% with PEG-IFNalpha-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 mug q2wk versus PEG-IFNalpha-2a (1.1 versus 4.3 days; P = 0.006).


CONCLUSIONS
Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFNalpha-2a.
Zeuzem
Stefan
S
JW Goethe-University Hospital, Frankfurt, Germany. zeuzem@em.uni-frankfurt.de
Yoshida
Eric M
EM
Benhamou
Yves
Y
Pianko
Stephen
S
Bain
Vincent G
VG
Shouval
Daniel
D
Flisiak
Robert
R
Rehak
Vratislav
V
Grigorescu
Mircea
M
Kaita
Kelly
K
Cronin
Patrick W
PW
Pulkstenis
Erik
E
Subramanian
G Mani
GM
McHutchison
John G
JG
D000284:Administration, Oral; D000328:Adult; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006304:Health Status; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011788:Quality of Life; D012367:RNA, Viral / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C531108:albinterferon alfa-2b; C100416:peginterferon alfa-2a