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J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.

Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent.

Author information

1
Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain. Electronic address: xforns@clinic.ub.es.
2
Henry Ford Health System, Detroit, MI, USA.
3
Carmel Medical Center, Haifa, Israel.
4
The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
5
Servicio de Gastroenterología y Hepatología, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain.
6
Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
7
Merck and Co., Inc., Kenilworth, NJ, USA.
8
Hospital Universitario Valle Hebron and Ciberehd, Barcelona, Spain.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02105454.

KEYWORDS:

C-SALVAGE; Direct-acting antiviral agents; Elbasvir; Grazoprevir; HCV genotype-1

PMID:
25895428
DOI:
10.1016/j.jhep.2015.04.009
[Indexed for MEDLINE]

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