Journal
JOURNAL OF HEPATOLOGY
Volume 63, Issue 3, Pages 564-572Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2015.04.009
Keywords
C-SALVAGE; HCV genotype-1; Grazoprevir; Elbasvir; Direct-acting antiviral agents
Categories
Funding
- Janssen
- Abbvie
- Bristol-Myers Squibb
- Gilead
- GlaxoSmithKline
- Intercept
- Merck
- Vertex
- MSD
- BMS
- Amgen
- CVS Caremark
- Novartis
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Background & Aims: The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy. Methods: C-SALVAGE was an open-label study of grazoprevir 100 mg and elbasvir 50 mg QD with weight-based ribavirin BID for 12 weeks in cirrhotic and non-cirrhotic patients with chronic HCV genotype-1 infection who had not attained SVR after >= 4 weeks of peginterferon and ribavirin plus either boceprevir, telaprevir, or simeprevir. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, and HIV or HBV co-infection. The primary efficacy outcome was SVR12 defined as a HCV RNA level below the assay limit of quantification 12 weeks after the end of treatment. Results: Of the 79 patients treated with >= 1 dose of study drug, 66 (84%) patients had a history of virologic failure on a regimen containing a NS3/4A protease inhibitor; 12 of the other 13 patients discontinued prior treatment because of adverse experiences. At entry, 34 (43.6%) of 78 evaluable patients harbored NS3 RAVs. SVR12 rates were 76/79 (96.2%) overall, including 28/30 (93.3%) patients with genotype 1a infection, 63/66 (95.5%) patients with prior virologic failure, 43/43 (100%) patients without baseline RAVs, 31/34 (91.2%) patients with baseline NS3 RAVs, 6/8 (75.0%) patients with baseline NS5A RAVs, 4/6 66.7%) patients with both baseline NS3 and RAVs, and 32/34 (94.1%) cirrhotic patients. None of the five reported serious adverse events were considered drug-related. Conclusions: Grazoprevir and elbasvir plus ribavirin for 12 weeks provides a promising new treatment option for patients after failure of triple therapy containing an earlier-generation protease inhibitor. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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