Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia

Abstract

Aim: To evaluate addition of boceprevir to peginterferon/ribavirin (PR) in Russian patients with chronic hepatitis C virus (HCV).

Methods: Treatment-naive (TN) and treatment-experienced (TE) patients (who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebo-controlled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. TN patients randomized to triple therapy received boceprevir (800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8 (TW8) HCV RNA levels. TE patients received boceprevir plus PR for 32 wk and then further therapy according to TW8 HCV RNA levels. Treatment was discontinued for TN patients with detectable HCV RNA at TW24 and TE patients with detectable HCV RNA at TW12 because of futility. The primary efficacy end point was sustained virologic response (SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy.

Results: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2% (95%CI: 16.4-41.5; P < 0.0001). Rates of SVR were higher in the boceprevir arm in both TN and TE patient groups (TN 78.4% vs 56.3%; TE 69.4% vs 30.0%). Within TE patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type (null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both TN (86%) and TE (71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone (47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia (< 10 g/dL) and those without anemia (71.2% vs 77.4%).

Conclusion: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.

Keywords: Boceprevir; Clinical trial; Hepatitis C virus; Peginterferon; Randomized; Ribavirin; Sustained virologic response.

Figures

Figure 1

Study design. BOC: Boceprevir; D/c: Discontinued; HCV: Hepatitis C virus; PR: Peginterferon/ribavirin; TW: Treatment week.

Figure 2

Patient disposition. BOC: Boceprevir; PR: Peginterferon/ribavirin.

Figure 3

Analysis of sustained virologic response, end of treatment response, and relapse rate. If a patient had missing data at and after the FW24 window and had undetectable HCV RNA at FW12, the patient was considered a sustained virologic responder. The P value was adjusted for stratification factors of IL28B genotype (CC vs non-CC) and previous treatment (TN vs TE), based on the Miettinen and Nurminen method. EOT was defined as the last dose date in treatment phase ± 14 d inclusive. The closest value to the last dose date was considered to be the EOT value. If there was no value within this window, the closest available value after this window was used. Relapse was defined as any patient who had detectable HCV RNA following end of all study therapy, after becoming undetectable and remaining so until end of treatment. EOT: End of treatment; HCV: Hepatitis C virus; PR: Peginterferon/ribavirin; SVR: Sustained virologic response; TE: Treatment experienced; TN: Treatment naive; IL28B: Interleukin-28B.