Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1 infection.
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).
Auckland Clinical Studies, Auckland, New Zealand. edgane@adhb.govt.nz.
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Gane
Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Ben Ari
Fremantle Hepatitis Services, Fremantle Hospital, Fremantle, WA, Australia.
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Mollison
Liver Unit, Carmel Medical Center Technion Faculty of Medicine, Haifa, Israel.
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Zuckerman
Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
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Bruck
Liver Unit, Rambam Healthcare Campus and the Technion Faculty of Medicine, Haifa, Israel.
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Baruch
Merck & Co., Inc., Kenilworth, NJ, USA.
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Howe
Merck & Co., Inc., Kenilworth, NJ, USA.
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Wahl
Merck & Co., Inc., Kenilworth, NJ, USA.
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Bhanja
Merck & Co., Inc., Kenilworth, NJ, USA.
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Hwang
Merck & Co., Inc., Kenilworth, NJ, USA.
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Zhao
Merck & Co., Inc., Kenilworth, NJ, USA.
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Robertson
D000328:Adult; D000577:Amides; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D003521:Cyclopropanes; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D047029:Lactams, Macrocyclic
D000577:Amides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D011810:Quinoxalines; D012254:Ribavirin; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic
adverse event; clinical trial; efficacy; randomized; resistance