Controlled release recombinant human interferon-α2b for treating patients with chronic hepatitis C genotype 1: a phase 2a clinical trial

Better convenience and tolerability and sustained therapeutic concentrations might improve interferon (IFN) treatment for chronic hepatitis C virus (HCV) infection. In an open‐label, randomized study, controlled release free (chemically unmodified) recombinant human IFN‐α2b in poly(ether–ester) microspheres (CR‐rhIFN‐α2b), was injected at doses of 160, 320, 480 or 640 μg every 2 weeks for 12 weeks with concomitant weight‐based oral ribavirin in 32 treatment‐naïve patients with chronic HCV genotype 1. Treatment was well tolerated, with 31 patients (97%) successfully completing the study. Full doses of CR‐rhIFN‐α2b were administered on 96% of scheduled occasions. Flu‐like symptoms were generally mild and brief. Injection site reactions developed in 13 patients (41%), and neutropenia occurred in six of eight patients receiving 640 μg. In the 320, 480 and 640 μg groups, 62–75% of patients achieved a ≥2 log10 HCV RNA reduction by 4 weeks and 88–100% by 12 weeks. For those groups, the pooled median time to ≥2 log10 reduction was 11 days (95% confidence interval, 7–35 days). In those groups, viral reduction below the limit of detection was accomplished in 25% of patients by 4 weeks and in 62% by 12 weeks. The 160‐μg dose was less potent. After CR‐rhIFN‐α2b injection, stable plateau levels of serum IFN‐α2b were generally reached within 72 h. Treatment‐emergent neutralizing antibodies to IFN‐α2b were observed in one patient. No antibodies to host plant proteins were detected. CR‐rhIFN‐α2b with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1.