Efficacy and safety of simeprevir with PegIFN/ribavirin in naïve or experienced patients infected with chronic HCV genotype 4

J Hepatol. 2015 May;62(5):1047-55. doi: 10.1016/j.jhep.2014.12.031. Epub 2015 Jan 14.

Abstract

Background & aims: Simeprevir (SMV) is a once-daily (QD), oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of genotype (GT) 1 and GT4 infection. This Phase III, open-label, single-arm study (RESTORE; NCT01567735) evaluated efficacy/safety of SMV with peginterferon-α-2a/ribavirin (PR) in patients with chronic HCV GT4 infection.

Methods: 107 patients were included. Treatment-naïve (n=35) and prior relapse patients (n=22) received SMV 150mg QD+PR (12 weeks), followed by PR alone (12 or 36 weeks, response-guided [HCV RNA <25IU/ml detectable/undetectable at week 4 and <25IU/ml undetectable at week 12]). Prior non-responders (partial, n=10; null, n=40) received SMV/PR (12 weeks), followed by PR for 36 weeks. The primary endpoint was sustained virologic response 12 weeks after end of treatment (SVR12).

Results: Median age: 49.0years; 28.0% Black/African; 7.5% IL28B CC; 28.8% METAVIR F4. Overall, 65.4% (70/107) of patients achieved SVR12 (82.9% [29/35] treatment-naïve; 86.4% [19/22] prior relapsers; 60.0% [6/10] prior partial responders; 40.0% [16/40] prior null responders). In treatment-naïve and prior relapser patients fulfilling response-guided criteria for 24 weeks of treatment (88.6% [31/35] and 90.9% [20/22]), SVR12 rates were high: 93.5% [29/31] and 95.0% [19/20], respectively. Overall on-treatment failure and relapse rates were 23.4% (25/107) and 14.6% (12/82), respectively. Adverse events (AEs) were mainly grade 1/2; serious AEs were infrequent (4.7%) and considered unrelated to SMV.

Conclusions: Efficacy and safety of SMV 150mg QD for 12 weeks with PR in treatment-naïve or -experienced patients with chronic HCV GT4 infection were in line with previous reports for HCV GT1 infection.

Keywords: Chronic; Efficacy; Genotype 4; Hepatitis C virus; Protease inhibitor; Response-guided; Safety; Simeprevir; Sustained virologic response; TMC435 (10/10).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Drug Administration Schedule
  • Drug Therapy, Combination / methods
  • Female
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / ethnology
  • Hepatitis C, Chronic* / virology
  • Humans
  • Interferon-alpha* / administration & dosage
  • Interferon-alpha* / adverse effects
  • Male
  • Middle Aged
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / adverse effects
  • RNA, Viral / analysis
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Ribavirin* / administration & dosage
  • Ribavirin* / adverse effects
  • Secondary Prevention
  • Simeprevir* / administration & dosage
  • Simeprevir* / adverse effects
  • Treatment Outcome
  • Viral Load / drug effects
  • Viral Load / methods

Substances

  • Antiviral Agents
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Simeprevir
  • peginterferon alfa-2a