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-IFNα)-2a 180 μg one time per week (qwk), or alb-IFN 900 or 1,200 μg once every two weeks (q2wk), or 1,200 μg 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 μg q2wk, 55.5% (61/110) with 1,200 μg q2wk, and 50.9% (59/116) with 1,200 μg q4wk, and 57.9% (66/114) with PEG-IFNα-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 μg q2wk, 18.2% with 1,200 μg q2wk and 12.1% with 1,200 μg q4wk, and 6.1% with PEG-IFNα-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 μg q2wk versus PEG-IFNα-2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFNα-2a. (HEPATOLOGY 2008;48:407–417.)