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Clinical Trial
. 2017 Jan 5;12(1):e0168713.
doi: 10.1371/journal.pone.0168713. eCollection 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  1 , Christophe Moreno  2 , Christoph Sarrazin  3 , Michael Gschwantler  4 , Graham R Foster  5 , Antonio Craxí  6 , Peter Buggisch  7 , Faisal Sanai  8 , Ceyhun Bicer  9 , Oliver Lenz  9 , Gino Van Dooren  9 , Catherine Nalpas  10 , Isabelle Lonjon-Domanec  10 , Michael Schlag  11 , Maria Buti  12
Affiliations
Clinical Trial

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 et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: T. Asselah has served as a consultant/speaker for AbbVie, Achillion, Boehringer-Ingelheim, BMS, Gilead, Janssen, Merck, and Roche. C. Moreno has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead, Janssen Pharmaceuticals and Promethera. He has received research grants from Abbvie, Astellas, Gilead Sciences, Janssen Pharmaceuticals, Novartis and Roche. C. Sarrazin has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, and Qiagen. He has received research grants from Abbott, Gilead Sciences, Janssen Pharmaceuticals, Roche, Qiagen. M Gschwantler has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen Pharmaceuticals, Merck Sharpe & Dohme and Roche. GR Foster has been a paid speaker or adviser for Abbvie, Bristol-Myers Squibb, Gilead Sciences, GSK, Janssen Pharmaceuticals, Merck Sharpe & Dohme and Roche. He has received research grants from Gilead Sciences and Springbank. A Craxí has no conflicts of interest. P Buggisch has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe and Dohme and Roche. M Buti has been a paid speaker or adviser for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme, and Novartis. She has been a lecturer for Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme, and Novartis. She has been a clinical investigator for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, and Roche. F Sanai has served as a consultant/speaker for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck and Roche, and has received research grants from Bristol-Myers Squibb and Roche. C Bicer, O Lenz, G van Dooren, C Nalpas, I Lonjon-Domanec, M Schlag are employees of Janssen Pharmaceuticals and may be Johnson & Johnson stockholders. This does not alter our adherence to PLoS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Patient Disposition Flow Chart for Patients with HCV GT4.
Fig 2
Fig 2. Eligibility for 12-week simeprevir plus PR regimen according to patient baseline characteristics.
Fig 3
Fig 3. SVR12 among patients with HCV GT4 in the 12-week treatment group.
See this image and copyright information in PMC

References

    1. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C. September 2016. Available at: http://www.easl.eu/medias/cpg/HCV2016/English-report.pdf [last accessed 22 November 2016]. - PubMed
    1. Shiffman ML, Long AG, James A, Alexander P. My treatment approach to chronic hepatitis C virus. Mayo Clin Proc. 2014; 89:934–42. 10.1016/j.mayocp.2014.04.013 - DOI - PubMed
    1. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 2014; 59:318–27. 10.1002/hep.26744 - DOI - PMC - PubMed
    1. Tapper EB, Afdhal NH. Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3. J Vir Hepat. 2013; 20:669–77. - PubMed
    1. Khattab MA, Ferenci P, Hadziyannis SJ, Colombo M, Manns MP, Almasio PL, et al. Management of hepatitis C virus genotype 4: recommendations of an international expert panel. J Hepatol. 2011; 54:1250–62. 10.1016/j.jhep.2010.11.016 - DOI - PubMed

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