Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial.

Abstract

BACKGROUND & AIMS:

Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV.

METHODS:

We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point.

RESULTS:

Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P < .001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo.

CONCLUSIONS:

In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.

• Authors: Stefan Zeuzem, Thomas Berg, Edward Gane, Peter Ferenci, Graham R Foster, Michael W Fried, Christophe Hezode, Gideon M Hirschfield, Ira Jacobson, Igor Nikitin, Paul J Pockros, Fred Poordad, Jane Scott, Oliver Lenz, Monika Peeters, Vanitha Sekar, Goedele De Smedt, Rekha Sinha, Maria Beumont-Mauviel
• Journal: Gastroenterology (Gastroenterology) Vol. 146 Issue 2 Pg. 430-41.e6 (Feb 2014) ISSN: 1528-0012 [Electronic] United States
• PMID: 24184810 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Heterocyclic Compounds, 3-Ring
• Interferon-alpha
• Recombinant Proteins
• Sulfonamides
• Polyethylene Glycols
• Ribavirin
• Simeprevir
• peginterferon alfa-2a

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Heterocyclic Compounds, 3-Ring (therapeutic use)
• Humans
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Simeprevir
• Sulfonamides (therapeutic use)
• Treatment Outcome
• Viral Load
• Young Adult