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Phase 2a Study to Evaluate the Safety and Tolerability and Anti-Viral Effect of 4 Doses of a Novel, Controlled-Release Interferon Alfa-2b (LocteronTM) Given Every 2 Weeks for 12 Weeks in Treatment-Naïve Patients with Chronic Hepatitis C (Genotype 1) (AASLD 2007)
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AASLD 2007
Reported by Jules Levin
I. Dzublyk1; T. Yegorova1; L. Moroz2; O. Popovych2; I. Zaytsev3; V. Miroshnichenko3; E. Herrmann4; S. Zeuzem4; E. van Hoogdalem5; J. Humphries6; 1National Medical Academy, Kiev, Ukraine; 2National Medical University, Vinnitsa, Ukraine; 3State
Medical University, Donetsk, Ukraine; 4Saarland University, Homburg/Saar, Germany; 5OctoPlus, N.V., Leiden, Netherlands; 6Biolex Therapeutics, Inc, Pittsboro, NC, USA
AUTHOR CONCLUSIONS
In this study, LocteronTM, a controlled-release formulation of unmodified IFN alfa-2b, administered every 2 weeks to treatment-naïve patients with chronic
hepatitis C (genotype 1) demonstrated strong anti-viral activity combined with an improved safety and tolerability profile compared to currently marketed IFNs and those in development.
Viral kinetic analysis demonstrated a dose- dependent anti-viral efficiency
during the entire 12-week treatment period.
INTRODUCTION
Controlled-release recombinant interferon alfa-2b (LocteronTM) is a novel approach to delivery of interferon (IFN) given every 2 weeks offering an improved tolerability combined with a high level of hepatitis C virus (HCV) RNA reduction in this trial .
STUDY OBJECTIVE
A phase 2a, open-label randomized, dose-ranging study was conducted in
treatment-naïve patients with genotype 1 chronic HCV infection to evaluate
the safety, tolerability and anti-viral effect of LocteronTM.
METHODS
Thirty-two patients were randomized to receive subcutaneous injections of LocteronTM 14 days apart over 12 weeks in 4 dose cohorts (8 per cohort) of 160, 320, 480 and 640 µg, with the 640 µg group starting after safety evaluation of the other cohorts. All subjects received weight-based ribavirin.
Analysis of IFN-alpha2b in human serum samples was performed by a modified ELISA from GE HealthCare, UK, using standards and quality controls prepared from IFN-alpha2b (BLX-883). LLOQ for IFN-alpha2b using the ELISA was 2.5 pg/mL (A. Kromminga, IPM, Hamburg, Germany). HCV RNA assay was performed using COBAS TaqMan with an LLOQ of 28 IU/mL.
Viral kinetics were modeled mathematically from a full PK-PD model according to the individual pharmacokinetic profile of LocteronTM for all patients. The compartmental model was based on a differential equation system including a time-varying efficiency factor ε according to the respective serum levels of LocteronTM.
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