A therapeutic dose and its pharmacokinetics of ropeginterferon Alfa-2b for hepatitis C treatment

Abstract

Aim: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg. Methods: Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. Results: Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL−1. AUClast was 9364.292 h∗ng mL−1 and AUCinf was 11084.317 h∗ng mL−1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL−1. Conclusion: Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

Keywords

• Clinical trial
• Hepatitis C virus genotype 2
• Pegylated interferon