Grazoprevir-Elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: A randomized trial

Stefan Zeuzem, Reem Ghalib, K. Rajender Reddy, Paul J. Pockros, Ziv Ben Ari, Yue Zhao, Deborah D. Brown, Shuyan Wan, Mark J. DiNubile, Bach Yen Nguyen, Michael N. Robertson, Janice Wahl, Eliav Barr, Joan R. Butterton

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Novel interferon-and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. Objective: To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. Design: Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467) Setting: 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. Patients: Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. Intervention: Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. Measurements: Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. Results: Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI,-5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). Limitation: The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. Conclusion: Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalAnnals of Internal Medicine
Volume163
Issue number1
DOIs
StatePublished - 7 Jul 2015
Externally publishedYes

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