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

J Hepatol 2015 Sep 18;63(3):564-72. Epub 2015 Apr 18.

Hospital Universitario Valle Hebron and Ciberehd, Barcelona, Spain.

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.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S01688278150029
Publisher Site
http://dx.doi.org/10.1016/j.jhep.2015.04.009DOI Listing
September 2015
46 Reads

Publication Analysis

Top Keywords

patients baseline
16
patients
14
hcv genotype-1
12
ns3 ravs
12
chronic hcv
12
genotype-1 infection
12
protease inhibitor
12
ns3/4a protease
8
grazoprevir elbasvir
8
virologic failure
8
baseline ns3
8
patients chronic
8
elbasvir ribavirin
8
ribavirin
5
ravs
5
defined hcv
4
svr12 defined
4
level assay
4
rna level
4
grazoprevir
4

Similar Publications