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-alpha(2b) in poly(ether-ester) microspheres (CR-rhIFN-alpha(2b)), was injected at doses of 160, 320, 480 or 640 mu g every 2 weeks for 12 weeks with concomitant weight-based oral ribavirin in 32 treatment-naive patients with chronic HCV genotype 1. Treatment was well tolerated, with 31 patients (97%) successfully completing the study. Full doses of CR-rhIFN-alpha(2b) 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 mu g. In the 320, 480 and 640 mu g groups, 62-75% of patients achieved a >= 2 log(10) HCV RNA reduction by 4 weeks and 88-100% by 12 weeks. For those groups, the pooled median time to >= 2 log(10) 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-mu g dose was less potent. After CR-rhIFN-alpha(2b) injection, stable plateau levels of serum IFN-alpha(2b) were generally reached within 72 h. Treatment-emergent neutralizing antibodies to IFN-alpha(2b) were observed in one patient. No antibodies to host plant proteins were detected. CR-rhIFN-alpha(2b) with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1.