Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection

Mark Sulkowski, J. J. Feld, E. Lawitz, F. Felizarta, A. M. Corregidor, O. Khalid, R. Ghalib, W. B. Smith, V. Van Eygen, D. Luo, L. Vijgen, M. Gamil, T. N. Kakuda, S. Ouwerkerk-Mahadevan, P. Van Remoortere, M. Beumont

Research output: Contribution to journalArticle

Abstract

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalJournal of Viral Hepatitis
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2018

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Hepacivirus
Fibrosis
Genotype
Safety
Infection
Therapeutics
Pharmacokinetics
BMS-790052
Simeprevir
Sofosbuvir
Recurrence
Lost to Follow-Up
Chronic Hepatitis C
Treatment Failure
Drug Interactions
Antiviral Agents
Pharmaceutical Preparations

Keywords

  • cirrhotic
  • direct-acting antivirals
  • noncirrhotic
  • treatment-naïve
  • virologic response

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. / Sulkowski, Mark; Feld, J. J.; Lawitz, E.; Felizarta, F.; Corregidor, A. M.; Khalid, O.; Ghalib, R.; Smith, W. B.; Van Eygen, V.; Luo, D.; Vijgen, L.; Gamil, M.; Kakuda, T. N.; Ouwerkerk-Mahadevan, S.; Van Remoortere, P.; Beumont, M.

In: Journal of Viral Hepatitis, Vol. 25, No. 6, 01.06.2018, p. 631-639.

Research output: Contribution to journalArticle

Sulkowski, M, Feld, JJ, Lawitz, E, Felizarta, F, Corregidor, AM, Khalid, O, Ghalib, R, Smith, WB, Van Eygen, V, Luo, D, Vijgen, L, Gamil, M, Kakuda, TN, Ouwerkerk-Mahadevan, S, Van Remoortere, P & Beumont, M 2018, 'Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection', Journal of Viral Hepatitis, vol. 25, no. 6, pp. 631-639. https://doi.org/10.1111/jvh.12853
Sulkowski, Mark ; Feld, J. J. ; Lawitz, E. ; Felizarta, F. ; Corregidor, A. M. ; Khalid, O. ; Ghalib, R. ; Smith, W. B. ; Van Eygen, V. ; Luo, D. ; Vijgen, L. ; Gamil, M. ; Kakuda, T. N. ; Ouwerkerk-Mahadevan, S. ; Van Remoortere, P. ; Beumont, M. / Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. In: Journal of Viral Hepatitis. 2018 ; Vol. 25, No. 6. pp. 631-639.
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