title: Controlled release recombinant human interferon-α2b for treating patients with chronic hepatitis C genotype 1: a phase 2a clinical trial.
abstract: 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-α(2b) in poly(ether-ester) microspheres (CR-rhIFN-α(2b)), 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-α(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 μg. In the 320, 480 and 640 μg 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-μg dose was less potent. After CR-rhIFN-α(2b) injection, stable plateau levels of serum IFN-α(2b) were generally reached within 72 h. Treatment-emergent neutralizing antibodies to IFN-α(2b) were observed in one patient. No antibodies to host plant proteins were detected. CR-rhIFN-α(2b) with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1.
authors.affiliation: City Clinical Hospital 5, Department of Virology, Kiev, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Dzyublyk
authors.forename: T
authors.initials: T
authors.lastname: Yegorova
authors.forename: L
authors.initials: L
authors.lastname: Moroz
authors.forename: O
authors.initials: O
authors.lastname: Popovych
authors.forename: I
authors.initials: I
authors.lastname: Zaytsev
authors.forename: V
authors.initials: V
authors.lastname: Miroshnichenko
authors.forename: A
authors.initials: A
authors.lastname: Kromminga
authors.forename: M M
authors.initials: MM
authors.lastname: Wilkes
authors.forename: E J
authors.initials: EJ
authors.lastname: van Hoogdalem
authors.forename: J E
authors.initials: JE
authors.lastname: Humphries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin