Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment‐naïve patients with hepatitis C virus genotype 1 infection |
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| Authors: | E. Gane Z. Ben Ari L. Mollison E. Zuckerman R. Bruck Y. Baruch J. Wahl S. Bhanja P. Hwang Y. Zhao M. N. Robertson |
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| Affiliation: | 1. Auckland Clinical Studies, Auckland, New Zealand;2. Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel;3. The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;4. Fremantle Hepatitis Services, Fremantle Hospital, Fremantle, WA, Australia;5. Liver Unit, Carmel Medical Center Technion Faculty of Medicine, Haifa, Israel;6. Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;7. Liver Unit, Rambam Healthcare Campus and the Technion Faculty of Medicine, Haifa, Israel;8. Merck & Co., Inc., Kenilworth, NJ, USA |
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| Abstract: | Grazoprevir (GZR) is a second‐generation hepatitis C virus NS3/4A protease inhibitor. The aim of this study was to evaluate GZR plus ribavirin (RBV) in patients with HCV GT1 infection. Noncirrhotic, IL28B CC patients with HCV genotype 1 infection were randomized to GZR 100 mg once daily and RBV for 12 or 24 weeks. Patients in the 12‐week arm with detectable HCV RNA at treatment week 4 (TW4) had treatment extended to 24 weeks (response‐guided therapy, RGT). The primary endpoint was sustained virologic response (SVR12) at follow‐up week 12 (HCV RNA <25 IU/mL) in the per‐protocol (PP) population (excluding patients with important protocol deviations). Twenty‐six patients were randomized and 22 were included in the PP population. SVR12 was 58.3% (7 of 12) and 90% (9 of 10) in the RGT and 24‐week arms, respectively. Seven PP patients had virologic failure, including one patient in the 24‐week arm who relapsed after follow‐up week 12. All three breakthrough patients had wild‐type (WT) virus at baseline and developed breakthrough at TW6 or TW12 with Y56H, A156T and D168A/N mutations. Of the five relapse patients, four had WT at baseline (at relapse three had WT and one had V55A and D168A), and one had S122A/T at baseline and S122T at relapse. There were no serious adverse events (AEs), discontinuations due to AEs or grade 3/4 elevations in total and/or direct bilirubin. Grazoprevir plus RBV was associated with a rapid and sustained suppression of HCV RNA. These results support further evaluation of grazoprevir‐based regimens (NCT01716156; protocol P039). |
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| Keywords: | adverse event clinical trial efficacy randomized resistance |
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