Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders

Anna S. Lok, David F. Gardiner, Christophe Hézode, Eric J. Lawitz, Marc Bourlière, Gregory T. Everson, Patrick Marcellin, Maribel Rodriguez-Torres, Stanislas Pol, Lawrence Serfaty, Timothy Eley, Shu Pang Huang, Jianling Li, Megan Wind-Rotolo, Fei Yu, Fiona McPhee, Dennis M. Grasela, Claudio Pasquinelli

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Background & Aims Patients with chronic hepatitis C virus (HCV) infection and prior null response (<2 log HCV RNA decline after ≥12 weeks of PegIFN/RBV) have limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir in non-cirrhotic genotype 1 null responders. Methods In this randomized, phase 2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60 mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200 mg) twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir twice-daily plus ribavirin (TRIPLE B3). The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (sustained virologic response, SVR12). Results Across all groups, mean HCV RNA was ≥6 log IU/ml, and 99% of patients had a non-CC IL28B genotype. SVR 12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2). In B3, most genotype 1a patients experienced virologic breakthrough. The most common adverse events were headache, diarrhea, and asthenia. Grade 3-4 aminotransferase elevations were infrequent and not treatment-limiting. Conclusions In genotype 1 null responders, daclatasvir plus twice-daily asunaprevir DUAL therapy is effective for most genotype 1b patients, and daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for genotype 1a patients. Interferon-free regimens including daclatasvir and twice-daily asunaprevir for genotype 1 null responders should be tailored to subtype.

Original languageEnglish (US)
Pages (from-to)490-499
Number of pages10
JournalJournal of Hepatology
Volume60
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Direct-acting antiviral agents
  • HCV NS5A inhibitor
  • Hepatitis C treatment
  • Non-responders
  • Protease inhibitor
  • Sustained virologic response

ASJC Scopus subject areas

  • Hepatology

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  • Cite this

    Lok, A. S., Gardiner, D. F., Hézode, C., Lawitz, E. J., Bourlière, M., Everson, G. T., Marcellin, P., Rodriguez-Torres, M., Pol, S., Serfaty, L., Eley, T., Huang, S. P., Li, J., Wind-Rotolo, M., Yu, F., McPhee, F., Grasela, D. M., & Pasquinelli, C. (2014). Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders. Journal of Hepatology, 60(3), 490-499. https://doi.org/10.1016/j.jhep.2013.10.019