Randomized Controlled Trial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 28, 2016; 8(6): 331-339
Published online Feb 28, 2016. doi: 10.4254/wjh.v8.i6.331
Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia
Vasily Isakov, Igor Nikitin, Vladimir Chulanov, Pavel Ogurtsov, Ekaterina Lukyanova, Jianmin Long, Janice Wahl, Frans A Helmond, The P08160 Trial Investigators
Vasily Isakov, Department of Gastroenterology and Hepatology, Institute of Nutrition, Moscow 115446, Russia
Igor Nikitin, Department of Gastroenterology and Hematology, Russian Academy of Sciences, Moscow 117593, Russia
Vladimir Chulanov, Clinical Diagnostics and Research Center, Central Research Institute of Epidemiology, Moscow 111123, Russia
Pavel Ogurtsov, Hospital Medicine, Peoples’ Friendship University of Russia, Moscow 117198, Russia
Ekaterina Lukyanova, Medical Affairs, MSD Pharmaceuticals LLC, Moscow 115093, Russia
Jianmin Long, Janice Wahl, Frans A Helmond, Clinical Research, Merck & Co., Inc., Kenilworth, NJ 07033, United States
Author contributions: Isakov V, Long J, Wahl J and Helmand FA designed the study; Isakov V, Nikitin I, Chulano V and Ogurtsov P enrolled patients; Isakov V, Lukyanova E, Long J and Helmand FA analyzed the data; Isakov V and Helmand FA wrote the first draft; all authors critically reviewed and approved the final draft of the paper.
Supported by Merck & Co., Inc., Kenilworth, NJ, United States.
Institutional review board statement: The protocol P08160 of the study registered at ClinicalTrials.gov with identifier NCT01425203 presented in the manuscript of Isakov V et al “Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia” was reviewed and approved by the Institute of Nutrition (Moscow, Russia) Institutional Review Board.
Clinical trial registration statement: Protocol P08160 (The Effect of Boceprevir in Russian Participants Diagnosed with Chronic Hepatitis C Genotype 1) is registered at ClinicalTrials.gov (Identifier: NCT01425203).
Informed consent statement: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients included in the study.
Conflict-of-interest statement: Isakov V has received research/grant support from MSD, has served as a board member and or consultant for Abbvie, Vertex, Roche, Novartis, Janssen, and Bristol-Myers Squibb; has served on speakers’ bureaus for Bristol-Myers Squibb, Janssen, Roche, and Novartis; and has received travel funding from Bristol-Myers Squibb and MSD Russia. Chulanov V has served on advisory boards for Roche, Bristol-Myers Squibb, Janssen, Novartis, and MSD Russia; has received research grants from Bristol-Myers Squibb; and has served on speakers’ bureaus for Bristol-Myers Squibb, Roche, Janssen, Novartis, Gilead, AbbVie, and MSD. Ogurtsov P has served on advisory boards for Schering-Plough and delivered lectures on behalf of Abbott, Solvay, PRO.MED.CS Praha a.s., and Veropharm. Nikitin I has nothing to disclose. Lukyanova E, Long J, Wahl J and Helmond FA are current employees of Merck & Co., Inc., Kenilworth, NJ, United States.
Data sharing statement: These data were presented in part at the 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1-5, 2013; Washington, DC, United States.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vasily Isakov, Professor, Department of Gastroenterology and Hepatology, Institute of Nutrition, Kashirskoe Shosse 21, Moscow 115446, Russia. vasily.isakov@gmail.com
Telephone: +7-499-6130764 Fax: +7-499-6130764
Received: July 3, 2015
Peer-review started: July 3, 2015
First decision: August 26, 2015
Revised: October 7, 2015
Accepted: December 19, 2015
Article in press: December 23, 2015
Published online: February 28, 2016
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: Hepatitis C virus, Boceprevir, Peginterferon, Ribavirin, Randomized, Clinical trial, Sustained virologic response

Core tip: Compared to the standard-of care treatment with peginterferon and ribavirin (PR), addition of boceprevir to PR results in a significant increase in rates of sustained virologic response achieved with substantially shorter treatment durations across a broad cross-section of patients with chronic hepatitis C virus infection in Russia.