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Konstantin Zhdanov,1 Vasily Isakov,2 Eduard Burnevich,3 Svetlana Kizhlo,4 Igor Bakulin,5 Vadim Pokrovsky,6 Liwen Liang,7 Peggy Hwang,7 Rohit Talwani,7 Barbara A Haber,7 Michael N Robertson7 1Military Medical Academy n.a. S.M. Kirov, St. Petersburg, Russia; 2Department of Gastroenterology & Hepatology, Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow, Russia; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russia; 4City Center for AIDS and Infectious Diseases Treatment and Prophylaxis, St. Petersburg, Russia; 5I.I. Mechnikov North-Western State Medical University of the Ministry of Health of the Russian Federation, St. Petersburg, Russia; 6Department of AIDS, Central Research Institute of Epidemiology, Moscow, Russia; 7Merck & Co., Inc., Kenilworth, NJ, USACorrespondence: Barbara A HaberMerck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USATel +1 267-305-3729Email barbara.haber@merck.comPurpose: Hepatitis C virus (HCV) infection is a major healthcare concern in Russia, where almost 5 million individuals are viremic. Elbasvir/grazoprevir is a fixed-dose combination therapy for the treatment of HCV genotype 1 and genotype 4 infection. The present analysis aimed to assess the safety and efficacy of elbasvir/grazoprevir in individuals with HCV infection enrolled at Russian study sites in the C-CORAL study.Patients and Methods: C-CORAL (Protocol PN-5172-067; NCT02251990) was a Phase 3, placebo-controlled, double-blind study conducted throughout Asia and Russia. Treatment-naive participants with chronic HCV infection were randomly assigned to receive immediate or deferred treatment with elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks. Participants in the immediate-treatment group received elbasvir/grazoprevir for 12 weeks, and those in the deferred-treatment group received placebo for 12 weeks, followed by open-label elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12).Results: One hundred and nineteen Russian participants were randomized (immediate-treatment group, n=88; deferred-treatment group, n=31). Most participants were white (99%) with HCV genotype 1b infection (97%) and mild-to-moderate (F0–F2) fibrosis (70%). SVR12 was achieved by 98.9% participants in the immediate-treatment group and by 100% of those receiving deferred elbasvir/grazoprevir in the deferred-treatment group. One participant relapsed with nonstructural protein 5A (NS5A) L28M and Y93H resistance-associated substitutions at baseline and at time of failure. Drug-related adverse events were reported by 19% of participants receiving elbasvir/grazoprevir in the immediate-treatment group and by 16% of those receiving placebo in the deferred-treatment group. No serious adverse event or deaths occurred, and no participant discontinued treatment owing to an adverse event.Conclusion: Elbasvir/grazoprevir for 12 weeks was highly effective in treatment-naive Russian individuals with HCV genotype 1b infection.Keywords: hepatitis C, therapy, placebo, Russia, viral drug resistance |
