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.

Abstract

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 12 Issue 1 Pg. e0168713 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28056030 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• interferon-lambda, human
• Interferon-alpha
• Interleukins
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Interferons
• Simeprevir
• peginterferon alfa-2a

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (pathogenicity)
• Hepatitis C (drug therapy, metabolism)
• Humans
• Interferon-alpha (adverse effects, therapeutic use)
• Interferons
• Interleukins (genetics)
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Ribavirin (adverse effects, therapeutic use)
• Simeprevir (adverse effects, therapeutic use)
• Viral Load
• Young Adult