Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2-6: TMC435-C202, a phase IIa, open-label study.

Abstract

BACKGROUND & AIMS:

TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacokinetic profile that supports once daily dosing, and demonstrates potent antiviral activity. This phase IIa study (TMC435-C202; NCT00812331) was conducted to investigate the antiviral activity, safety, tolerability, and pharmacokinetics of TMC435 in treatment-naїve patients infected with HCV genotypes 2-6.

METHODS:

The study consisted of 7 days of monotherapy with TMC435 (200mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from day 8 with a follow-up period up to days 37-42.

RESULTS:

Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary end point at day 8, the mean (± standard error) change in plasma HCV ribonucleic acid (log(10)IU/ml) from baseline was the greatest for genotypes 6 (-4.35 ± 0.29) and 4 (-3.52 ± 0.43), followed by genotypes 2 (-2.73 ± 0.71) and 5 (-2.19 ± 0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period.

CONCLUSIONS:

The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated.

• Authors: Christophe Moreno, Thomas Berg, Tawesak Tanwandee, Satawat Thongsawat, Hans Van Vlierberghe, Stefan Zeuzem, Oliver Lenz, Monika Peeters, Vanitha Sekar, Goedele De Smedt
• Journal: Journal of hepatology (J Hepatol) Vol. 56 Issue 6 Pg. 1247-53 (Jun 2012) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 22326470 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Heterocyclic Compounds, 3-Ring
• Sulfonamides
• Simeprevir

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Female
• Genotype
• Hepacivirus (classification, genetics)
• Hepatitis C (drug therapy, virology)
• Heterocyclic Compounds, 3-Ring (adverse effects, pharmacokinetics, therapeutic use)
• Humans
• Male
• Middle Aged
• Simeprevir
• Sulfonamides (adverse effects, pharmacokinetics, therapeutic use)