1Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain. Electronic address: XFORNS@clinic.ub.es.
2Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
3J.W. Goethe University Hospital, Frankfurt, Germany.
4Auckland Hospital Clinical Studies Unit, Auckland, New Zealand.
5INSERM U954, Université de Lorraine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre Les Nancy, France.
6Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum, University of Bologna, Italy.
7Medical University of Warsaw, Wolska, Warsaw, Poland.
8Imperial College Healthcare NHS Trust, London, United Kingdom.
9Janssen Infectious Diseases BVBA, Beerse, Belgium.
10Janssen Research & Development, Beerse, Belgium.
11Janssen Global Services LLC, High Wycombe, UK.
12Janssen Global Services, LLC, Titusville, NJ, USA.
BACKGROUND & AIMS:
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 randomly assigned (2:1) to groups given simeprevir (150 mg, once daily) and PR (n=260) or placebo and PR (n=133) for 12 weeks. Patients were then 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% CI, 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 grade 1/2; 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 following interferon-based therapy, 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. ClinicalTrials.gov number: NCT01281839.