Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

Journal of Hepatology

Volumn 65, Issue 6, 2016, Pages 1112-1119

  Sperl, Jan ^a   Horvath, Gabor ^b   Halota, Waldemar ^c   Ruiz Tapiador, Juan Arenas ^d   Streinu Cercel, Anca ^e   Jancoriene, Ligita ^f   Werling, Klara ^g   Kileng, Hege ^h   Koklu, Seyfettin ⁱ   Gerstoft, Jan ^j   Urbanek, Petr ^k   Flisiak, Robert ^l   Leiva, Rafael ^m   Kazenaite, Edita ^f   Prinzing, Renate ⁿ   Patel, Sushma ⁿ   Qiu, Jingjun ⁿ   Asante Appiah, Ernest ⁿ   Wahl, Janice ⁿ   Nguyen, Bach Yen ⁿ   Barr, Eliav ⁿ   Platt, Heather L ⁿ   more..

^a INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE   (Czech Republic)

^b Budai Hepatológiai Centrum   (Hungary)

^c NICOLAUS COPERNICUS UNIVERSITY   (Poland)

^d HOSPITAL DONOSTIA   (Spain)

^e CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^f VILNIUS UNIVERSITY   (Lithuania)

^g SEMMELWEIS UNIVERSITY   (Hungary)

^h Universitetssykehuset Nord Norge   (Norway)

ⁱ HACETTEPE UNIVERSITY   (Turkey)

^j UNIVERSITY OF COPENHAGEN   (Denmark)

^k CHARLES UNIVERSITY   (Czech Republic)

^l MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

^m HAUKELAND UNIVERSITY HOSPITAL   (Norway)

ⁿ MERCK RESEARCH LABORATORIES   (United States)

more..

Author keywords

Hepatitis; Randomized; Therapy

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; CREATININE; DIAMORPHINE; ELBASVIR PLUS GRAZOPREVIR; HEMOGLOBIN; PEGINTERFERON; RIBAVIRIN; SOFOSBUVIR; VIRUS RNA; ANTIVIRUS AGENT; BENZOFURAN DERIVATIVE; IMIDAZOLE DERIVATIVE; INTERFERON; QUINOXALINE DERIVATIVE;

ABSCESS; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANEMIA; ANGINA PECTORIS; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BILIRUBIN BLOOD LEVEL; CEREBROVASCULAR ACCIDENT; CHILL; COMBINATION DRUG THERAPY; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; COUGHING; CREATININE BLOOD LEVEL; DECREASED APPETITE; DEPRESSION; DRUG ABUSE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; FEVER; FLU LIKE SYNDROME; FOLLOW UP; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HEPATITIS C; HEPATITIS C VIRUS GENOTYPE 1; HEPATITIS C VIRUS GENOTYPE 4; HUMAN; INFLUENZA; LIVER DISEASE; MAJOR CLINICAL STUDY; MALE; MYALGIA; NAUSEA; NEUTROPHIL COUNT; OPEN STUDY; PERIODONTAL ABSCESS; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RECTUM DISEASE; SIDE EFFECT; TREATMENT DURATION; TREATMENT RESPONSE; VIRUS LOAD; CHRONIC HEPATITIS C; CLINICAL TRIAL; GENOTYPE; HEPACIVIRUS;

ANTIVIRAL AGENTS; BENZOFURANS; DRUG THERAPY, COMBINATION; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; IMIDAZOLES; INTERFERONS; QUINOXALINES; RIBAVIRIN; RNA, VIRAL; SOFOSBUVIR;

EID: 84994718632     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2016.07.050     Document Type: Article

References (21)

1. [1] Shepard, C.W., Finelli, L., Alter, M.J., Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5 (2005), 558–567.
2. [2] AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with Hepatitis C virus. Hepatology 62 (2015), 932–954.
3. [3] European Association for Study of Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 63 (2015), 199–236.
4. [4] Streinu-Cercel, A., Hepatitis C in the interferon-free era. Germs, 3, 2013, 114.
5. [5] Zepatier [package insert]. 2016, Merck & Co. Inc., Whitehouse Station, NJ, USA.
6. [6] Summa, V., Ludmerer, S.W., McCauley, J.A., Fandozzi, C., Burlein, C., Claudio, G., et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother 56 (2012), 4161–4167.
7. [7] Coburn, C.A., Meinke, P.T., Chang, W., Fandozzi, C.M., Graham, D.J., Hu, B., et al. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem 8 (2013), 1930–1940.
8. [8] Lahser, F.C., Bystol, K., Curry, S., McMonagle, P., Xia, E., Ingravallo, P., et al. The combination of grazoprevir, a HCV NS3/4A protease inhibitor, and elbasvir, a HCV NS5A inhibitor, demonstrates a high genetic barrier to resistance in HCV genotype 1a replicons. Antimicrob Agents Chemother 60 (2016), 2954–2964.
9. [9] Rockstroh, J.K., Nelson, M., Katlama, C., Lalezari, J., Mallolas, J., Bloch, M., et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV 2 (2015), e319–e327.
10. [10] Roth, D., Nelson, D.R., Bruchfeld, A., Liapakis, A., Silva, M., Monsour, H. Jr, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 386 (2015), 1537–1545.
11. [11] Zeuzem, S., Ghalib, R., Reddy, K.R., Pockros, P.J., Ben Ari, Z., Zhao, Y., et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic HCV genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 163 (2015), 1–13.
12. [12] Dore, G.J., Altice, F., Litwin, A.H., Dalgard, O., Gane, E.J., Shibolet, O., et al. Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: a randomized trial. Ann Intern Med, 2016, 10.7326/M16-0816 [Epub ahead of print].
13. [13] Manns, M.P., Vierling, J.M., Bacon, B.R., Bruno, S., Shibolet, O., Baruch, Y., et al. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology 147 (2014), 366–376, e6.
14. [14] Reddy, K.R., Zeuzem, S., Zoulim, F., Weiland, O., Horban, A., Stanciu, C., et al. Simeprevir vs. telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double–blind, non-inferiority phase 3 trial. Lancet Infect Dis 15 (2015), 27–35.
15. [15] Dore, G.J., Conway, B., Luo, Y., Janczewska, E., Knysz, B., Liu, Y., et al. Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: the MALACHITE-I/II trials. J Hepatol 64 (2016), 19–28.
16. [16] Lawitz, E., Mangia, A., Wyles, D., Rodriguez-Torres, M., Hassanein, T., Gordon, S.C., et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 368 (2013), 1878–1887.
17. [17] Lawitz, E., Gane, E., Pearlman, B., Tam, E., Ghesquiere, W., Guyader, D., et al. Efficacy and safety of 12 weeks vs. 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 385 (2015), 1075–1086.
18. [18] Sulkowski, M., Hezode, C., Gerstoft, J., Vierling, J.M., Mallolas, J., Pol, S., et al. Efficacy and safety of 8 weeks vs. 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 385 (2015), 1087–1097.
19. [19] Poynard, T., Colombo, M., Bruix, J., Schiff, E., Terg, R., Flamm, S., et al. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology 136 (2009), 1618–1628, e2.
20. [20] McHutchison, J.G., Lawitz, E.J., Shiffman, M.L., Muir, A.J., Galler, G.W., McCone, J., et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 361 (2009), 580–593.
21. [21] Bacon, B., Gordon, S.C., Lawitz, E., Marcellin, P., Vierling, J.M., Zeuzem, S., et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 364 (2011), 1207–1217.