PLoS ONE (Jan 2017)

Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response.

  • Tarik Asselah,
  • Christophe Moreno,
  • Christoph Sarrazin,
  • Michael Gschwantler,
  • Graham R Foster,
  • Antonio Craxí,
  • Peter Buggisch,
  • Faisal Sanai,
  • Ceyhun Bicer,
  • Oliver Lenz,
  • Gino Van Dooren,
  • Catherine Nalpas,
  • Isabelle Lonjon-Domanec,
  • Michael Schlag,
  • Maria Buti

DOI
https://doi.org/10.1371/journal.pone.0168713
Journal volume & issue
Vol. 12, no. 1
p. e0168713

Abstract

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BACKGROUND:HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12. METHODS:This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18-70 years with METAVIR F0-F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24. RESULTS:Of 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3-4 adverse events was lower in the 12-week group than in the 24-week group. CONCLUSIONS:Our findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study. TRIAL REGISTRATION:NCT01846832.