Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study

Xavier Forns, Marina Berenguer, Kerstin Herzer, Martina Sterneck, Maria Francesca Donato, Pietro Andreone, Stefano Fagiuoli, Tomasz Cieciura, Magdalena Durlik, Jose Luis Calleja, Zoe Mariño, Umesh Shukla, Thierry Verbinnen, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Monika Peeters, Katrien Janssen, Ronald Kalmeijer, Wolfgang Jessner

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. Methods: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). Results: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. Conclusion: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

Original languageEnglish
Article numbere12696
JournalTransplant Infectious Disease
Volume19
Issue number3
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Ribavirin
Hepacivirus
Liver Transplantation
Pharmacokinetics
Genotype
Safety
Infection
Cyclosporine
Therapeutics
Tacrolimus
Virus Diseases
BMS-790052
Simeprevir
Interferons
Clinical Trials
Transplants
Survival

Keywords

  • daclatasvir
  • hepatitis C virus
  • liver transplantation
  • ribavirin
  • simeprevir

ASJC Scopus subject areas

  • Transplantation
  • Infectious Diseases

Cite this

Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation : The Phase II SATURN study. / Forns, Xavier; Berenguer, Marina; Herzer, Kerstin; Sterneck, Martina; Donato, Maria Francesca; Andreone, Pietro; Fagiuoli, Stefano; Cieciura, Tomasz; Durlik, Magdalena; Calleja, Jose Luis; Mariño, Zoe; Shukla, Umesh; Verbinnen, Thierry; Lenz, Oliver; Ouwerkerk-Mahadevan, Sivi; Peeters, Monika; Janssen, Katrien; Kalmeijer, Ronald; Jessner, Wolfgang.

In: Transplant Infectious Disease, Vol. 19, No. 3, e12696, 01.06.2017.

Research output: Contribution to journalArticle

Forns, X, Berenguer, M, Herzer, K, Sterneck, M, Donato, MF, Andreone, P, Fagiuoli, S, Cieciura, T, Durlik, M, Calleja, JL, Mariño, Z, Shukla, U, Verbinnen, T, Lenz, O, Ouwerkerk-Mahadevan, S, Peeters, M, Janssen, K, Kalmeijer, R & Jessner, W 2017, 'Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study', Transplant Infectious Disease, vol. 19, no. 3, e12696. https://doi.org/10.1111/tid.12696
Forns, Xavier ; Berenguer, Marina ; Herzer, Kerstin ; Sterneck, Martina ; Donato, Maria Francesca ; Andreone, Pietro ; Fagiuoli, Stefano ; Cieciura, Tomasz ; Durlik, Magdalena ; Calleja, Jose Luis ; Mariño, Zoe ; Shukla, Umesh ; Verbinnen, Thierry ; Lenz, Oliver ; Ouwerkerk-Mahadevan, Sivi ; Peeters, Monika ; Janssen, Katrien ; Kalmeijer, Ronald ; Jessner, Wolfgang. / Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation : The Phase II SATURN study. In: Transplant Infectious Disease. 2017 ; Vol. 19, No. 3.
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abstract = "Background: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. Methods: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). Results: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-na{\"i}ve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91{\%} of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. Conclusion: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.",
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T1 - Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation

T2 - The Phase II SATURN study

AU - Forns, Xavier

AU - Berenguer, Marina

AU - Herzer, Kerstin

AU - Sterneck, Martina

AU - Donato, Maria Francesca

AU - Andreone, Pietro

AU - Fagiuoli, Stefano

AU - Cieciura, Tomasz

AU - Durlik, Magdalena

AU - Calleja, Jose Luis

AU - Mariño, Zoe

AU - Shukla, Umesh

AU - Verbinnen, Thierry

AU - Lenz, Oliver

AU - Ouwerkerk-Mahadevan, Sivi

AU - Peeters, Monika

AU - Janssen, Katrien

AU - Kalmeijer, Ronald

AU - Jessner, Wolfgang

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. Methods: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). Results: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. Conclusion: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

AB - Background: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. Methods: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). Results: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended. Conclusion: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

KW - daclatasvir

KW - hepatitis C virus

KW - liver transplantation

KW - ribavirin

KW - simeprevir

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