Lai Wei1, Ji Dong Jia2, Fu Sheng Wang3, Jun Qi Niu4, Xu Min Zhao5, Shengmei Mu5, Li Wen Liang5, Zaiqi Wang5, Peggy Hwang6, Michael N Robertson6, Paul Ingravallo6, Ernest Asante-Appiah6, Bo Wei6, Barbara Evans6, George J Hanna6, Rohit Talwani6, Zhong Ping Duan7, Konstantin Zhdanov8, Pin-Nan Cheng9, Tawesak Tanwandee10, Van Kinh Nguyen11, Jeong Heo12, Vasily Isakov13, Jacob George14. 1. Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing, China. 2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China. 3. Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China. 4. Department of Hepatology, First Hospital, Jilin University, Changchun, Jilin, China. 5. Merck Sharp & Dohme, Capital Medical University, Beijing, China. 6. Merck & Co., Inc., Kenilworth, New Jersey, USA. 7. Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. 8. Military Medical Academy n.a. S.M. Kirov, St. Petersburg, Russia. 9. National Cheng Kung University, Tainan, Taiwan. 10. Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. 11. National Hospital of Tropical Diseases, Hanoi, Vietnam. 12. College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. 13. Department of Gastroenterology and Hepatology, Federal Research Center of Nutrition and Biotechnology, Moscow, Russia. 14. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, New South Wales, Australia.
Abstract
BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS:Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.
RCT Entities:
BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS:C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS:Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.
Authors: Elise J Smolders; Anouk M E Jansen; Peter G J Ter Horst; Jürgen Rockstroh; David J Back; David M Burger Journal: Clin Pharmacokinet Date: 2019-10 Impact factor: 6.447
Authors: Konstantin Zhdanov; Vasily Isakov; Eduard Burnevich; Svetlana Kizhlo; Igor Bakulin; Vadim Pokrovsky; Liwen Liang; Peggy Hwang; Rohit Talwani; Barbara A Haber; Michael N Robertson Journal: Hepat Med Date: 2020-04-21