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Hepatology. 2015 Dec 24. doi: 10.1002/hep.28422. [Epub ahead of print]

Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A Phase 3 study (OPTIMIST-2).

Author information

  • 1Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
  • 2The Gastroenterology Group of South Jersey, Vineland, NJ.
  • 3Orlando Immunology Center, Orlando, FL, USA.
  • 4University of British Columbia, Vancouver, BC, Canada.
  • 5Private practice, Bakersfield, CA, USA.
  • 6Texas Clinical Research Institute, Arlington, TX, USA (Reem Ghalib MD).
  • 7University Hepatitis Center at Pointe West Infectious Diseases, Bradenton, FL, USA.
  • 8Quality Medical Research, Nashville, TN, USA.
  • 9Digestive Health Specialists, Winston-Salem, NC, USA.
  • 10Gastrointestinal Specialists of Georgia, Marietta, GA, USA.
  • 11Concorde Medical Group, New York, NY, USA.
  • 12South Denver Gastroenterology, P.C., Denver, CO, USA.
  • 13Janssen Research & Development LLC, Titusville, NJ, USA.
  • 14Janssen Infectious Diseases BVBA, Beerse, Belgium.
  • 15Janssen Global Services LLC, Titusville, NJ, USA.
  • 16Janssen Global Services LLC, High Wycombe, Buckinghamshire, UK.

Abstract

Hepatitis C virus (HCV)-infected patients with cirrhosis are historically a difficult-to-treat population and are at risk of hepatic decompensation. In the Phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor)+sofosbuvir (HCV nucleotide-analog NS5B polymerase inhibitor)±ribavirin for 12 or 24 weeks in HCV genotype (GT)1-infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This Phase 3, open-label, single-arm study (OPTIMIST-2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naïve or treatment-experienced patients with cirrhosis. Patients (aged 18-70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily (QD)+sofosbuvir 400 mg QD for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (HC; SVR12 rate of 70%). Safety and patient-reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir+sofosbuvir (83% [95% confidence interval 76-91%]) met the primary objective of superiority versus the HC (70%). SVR12 rates for treatment-naïve and treatment-experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events (AEs) occurred in 72 (70%) patients, with most (64%) being Grade 1 or 2. Serious AEs (none considered related to study treatment) occurred in 5 (5%) patients and 3 (3%) patients discontinued all study treatment due to AEs. Patient-reported outcomes improved from baseline to follow-up Week 12.

CONCLUSION:

Simeprevir+sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the HC in treatment-naïve and treatment-experienced HCV GT1-infected patients with cirrhosis and was generally safe and well tolerated. This article is protected by copyright. All rights reserved.

© 2015 by the American Association for the Study of Liver Diseases.

KEYWORDS:

HCV; clinical trial; direct-acting antiviral agents; efficacy; safety

PMID:
26704148
[PubMed - as supplied by publisher]
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