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

M. S. Sulkowski, J. J. Feld, E. Lawitz, F. Felizarta, A. M. Corregidor, O. Khalid, R. Ghalib, William 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

3 Citations (Scopus)

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

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Sulkowski, M. S., Feld, J. J., Lawitz, E., Felizarta, F., Corregidor, A. M., Khalid, O., ... Beumont, M. (2018). Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. Journal of Viral Hepatitis, 25(6), 631-639. https://doi.org/10.1111/jvh.12853

Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection. / Sulkowski, M. S.; Feld, J. J.; Lawitz, E.; Felizarta, F.; Corregidor, A. M.; Khalid, O.; Ghalib, R.; Smith, William; 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, MS, Feld, JJ, Lawitz, E, Felizarta, F, Corregidor, AM, Khalid, O, Ghalib, R, Smith, W, 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, M. S. ; Feld, J. J. ; Lawitz, E. ; Felizarta, F. ; Corregidor, A. M. ; Khalid, O. ; Ghalib, R. ; Smith, William ; 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.
@article{6f2cb5ebab04407ab0107266ecf3dca2,
title = "Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection",
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-na{\"i}ve 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-na{\"i}ve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.",
author = "Sulkowski, {M. S.} and Feld, {J. J.} and E. Lawitz and F. Felizarta and Corregidor, {A. M.} and O. Khalid and R. Ghalib and William Smith and {Van Eygen}, V. and D. Luo and L. Vijgen and M. Gamil and Kakuda, {T. N.} and S. Ouwerkerk-Mahadevan and {Van Remoortere}, P. and M. Beumont",
year = "2018",
month = "6",
day = "1",
doi = "10.1111/jvh.12853",
language = "English (US)",
volume = "25",
pages = "631--639",
journal = "Journal of Viral Hepatitis",
issn = "1352-0504",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection

AU - Sulkowski, M. S.

AU - Feld, J. J.

AU - Lawitz, E.

AU - Felizarta, F.

AU - Corregidor, A. M.

AU - Khalid, O.

AU - Ghalib, R.

AU - Smith, William

AU - Van Eygen, V.

AU - Luo, D.

AU - Vijgen, L.

AU - Gamil, M.

AU - Kakuda, T. N.

AU - Ouwerkerk-Mahadevan, S.

AU - Van Remoortere, P.

AU - Beumont, M.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047871994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047871994&partnerID=8YFLogxK

U2 - 10.1111/jvh.12853

DO - 10.1111/jvh.12853

M3 - Article

VL - 25

SP - 631

EP - 639

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

SN - 1352-0504

IS - 6

ER -