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Gastroenterology. 2014 Jun;146(7):1669-79.e3. doi: 10.1053/j.gastro.2014.02.051. Epub 2014 Mar 3.

Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial.

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Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. Electronic address:
Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
J.W. Goethe University Hospital, Frankfurt, Germany.
Auckland Hospital Clinical Studies Unit, Auckland, New Zealand.
INSERM U954, Université de Lorraine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre Les Nancy, France.
Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Medical University of Warsaw, Wolska, Warsaw, Poland.
Imperial College Healthcare National Health Service Trust, London, United Kingdom.
Janssen Infectious Diseases BVBA, Beerse, Belgium.
Janssen Research and Development, Beerse, Belgium.
Janssen Global Services, LLC, High Wycombe, United Kingdom.
Janssen Global Services, LLC, Titusville, New Jersey.



Simeprevir is an oral, once-daily inhibitor of hepatitis c virus (HCV) protease NS3/4A. We investigated the safety and efficacy of simeprevir with peg-interferon α-2a and ribavirin (PR) in a randomized, double-blind, placebo-controlled, phase 3 trial of patients with HCV genotype 1 infection who relapsed after previous interferon-based therapy.


Patients were assigned randomly (2:1) to groups given simeprevir (150 mg, once daily) and PR (n = 260) or placebo and PR (n = 133) for 12 weeks. Patients then were given PR alone for 12 or 36 weeks (simeprevir group, based on response-guided therapy criteria) or 36 weeks (placebo group).


Simeprevir and PR was significantly superior to placebo and PR; rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were 79.2% vs 36.1%, respectively (43.8% difference; 95% confidence interval, 34.6-53.0; P < .001). Among patients given simeprevir, 92.7% met the response-guided therapy criteria and were eligible to complete PR at week 24; of these, 83.0% achieved SVR12. HCV RNA was undetectable at week 4 in 77.2% of patients given simeprevir and 3.1% given placebo. On-treatment failure and relapse rates were lower among patients given simeprevir and PR than those given placebo and PR (3.1% vs 27.1%, and 18.5% vs 48.4%, respectively). Patients given simeprevir did not have adverse events beyond those that occurred in patients given PR alone. Most adverse events were grades 1/2; the prevalence of anemia and rash was similar in both groups. Patients in both groups reported similar severity of fatigue and functional impairments during the study, but duration was reduced among patients given simeprevir.


In a phase 3 trial of patients who had relapsed after interferon-based therapy, the addition of simeprevir to PR was generally well tolerated, with an SVR12 rate of 79.2%. Most patients (92.7%) receiving simeprevir were able to shorten therapy to 24 weeks. number: NCT01281839.


Chronic Hepatitis C; DAA; Drug; PROMISE

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