Narlaprevir, ritonavir, and sofosbuvir in non-cirrhotic chronic hepatitis C genotype 1 infected patients

Abstract

Aim of investigation - to estimate efficacy and safety of combination of direct-acting antivirus agents narlaprevir/ritonavir and sofosbuvir in patients with chronic hepatitis C.

Material and methods. Treatment naive, non-cirrhotic patients with chronic HCV infection (GT1) were enrolled at the study. Patients received therapy with the combination of narlaprevir 200 mg QD, ritonavir 100 mg QD and sofosbuvir 400 mg QD. Treatment duration was 12 weeks in group A and 8 weeks in group B. Preliminary results with rate of sustained virological response 12 weeks after treatment (SVR12) and main data of safety and tolerability of the investigating combination for all group A patients are presented.

Results and discussion. All 60 patients from group A reached SVR12 (100%; 95% CI 94-100%). Adverse events (AEs) during treatment period were registered in 28 (46.7%) patients. No serious AEs occurred. In total, treatment of narlaprevir/ritonavir and sofosbuvir combination during 12 weeks demonstrated high efficacy with good safety profile.

Keywords:chronic hepatitis C, hepatitis C virus, narlaprevir, ritonavir, sofosbuvir

Funding. The study is sponsored by the company R-Pharm JSC; the creation of basic documents, conducting research, processing the obtained data, statistical analysis, writing a report is carried out by the Contract Research Organization ALMEDIS.

Conflict of interests. The authors declare no conflict of interests.

For citation: Klimova E.A., Znoyko O.O., Chulanov V.P., Gusev D.A., Isakov V.A., Zhdanov K.V., Batskikh S.N., Kizhlo S.N., Mamonova N.A., Kozlov K.V., Sukachev V.S., Tarkhova E.P., Krasavina E.N., Samsonov M.Yu., Yushchuk N.D. Narlaprevir, ritonavir, and sofosbuvir in non-cirrhotic chronic hepatitis C genotype 1 infected patients. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2020; 9 (1): 50-6. doi: 10.33029/2305-3496-2020-9-1-50-56 (in Russian)

References

1. WHO Global health sector strategy on viral hepatitis 2016-2021. WHO/HIV/2016.06. http://www.who.int/hepatitis

2. WHO Global hepatitis report, 2017. Publication date: April 2017 Languages: English ISBN: 978-92-4-156545-5.

3. Pawlotsky J.M., Negro F., Aghemo A., Berenguer M., Dalgard O., Du-sheiko G., et al. EASL Recommendations on treatment of hepatitis C 2018. J Hepatol. 2018: 69 (2): 461-511. doi: 10.1016/j.jhep.2018.03.026.

4. Klimova E.A., Burnevich E.Z., Chulanov V.P., et al. Efficacy and safety of narlaprevir/ritonavir and daclatasvir non interferon combination in population of Russian patients with chronic hepatitis C. Terapevticheskiy arkhiv [Therapeutic Archive]. 2019; 91 (8): 67-74. doi: 10.26442/00403660.2019.08.000384 (in Russian)

5. Ivashkin V.T., Yuschuk N.D., eds. Recommendations for the diagnosis and treatment of adult patients with hepatitis C. Moscow: GEOTAR-Media; 2017. (in Russian)

6. Pimenov N.N., Komarova S.V., Karandashova I.V., Tsapkova N.N., Vol-chkova E.V., Chulanov V.P Hepatitis С and its outcomes in Russia: analysis of incidence, prevalence and mortality rates before the start of the programme of infection elimination. Infektsionnye bolezni [Infectious Diseases]. 2018; 16 (3): 37-45 (in Russian)

7. Arasappan A., Bennett F., Bogen S.L., et al. Discovery of narlaprevir (SCH 900518): a potent, second generation HCV NS3 serine protease inhibitor. ACS Med Chem Lett. 2010; 1 (2): 64-9. doi:10.1021/ml9000276

8. Reesink H., Bergmann J., de Bruijne J., Weegink C., van Lier J., van Vliet A., et al. Safety and antiviral activity of SCH 900518 administered as monotherapy and in combination with peginterferon alfa-2b to naive and treatment-experienced HCV-1-infected patients. J Hepatol. 2009; 50: S35-6. doi: 10.1016/S0168-8278(09)60088-X

9. Isakov V., Koloda D., Tikhonova N., Kikalishvili T., Krasavina E., Lek-ishvili K., et al. Pharmacokinetics of the new hepatitis C virus NS3 protease inhibitor narlaprevir following single-dose use with or without ritonavir in patients with liver cirrhosis. Antimicrob Agents Chemother. 2016; 60: 7098104. doi: 10.1128/AAC.01044-16

10. Mayevskaya M.V., Ivashkin V.T., Znoyko O.O., Klimova E.A., Abdurakhmanov D.T., Bakulin I.G., et al. Efficacy and safety of the Russian protease inhibitor narlaprevir at treatment-naive and earlier treated noncirrhotic patients with the 1st genotype chronic hepatitis C (PIONEER study). Rossiiskii Zhurnal Gastroenterologii, Gepatologii, Koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. 2017; 27 (6): 41-51. (in Russian)

11. Martinot-Peignoux M., Stern C., Maylin S., Ripault M.P., Boyer N., Leclere L., et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology. 2010; 51: 1122-6.

12. Thorlund K., Druyts E., Mills E.J. SVR12 is higher than SVR24 in treatment-naive hepatitis C genotype 1 patients treated with peginterferon plus ribavirin. Clinical Epidemiology 2014; 6: 49-58.

13. Wang X., Fan X., Deng H., Zhang X., Zhang K., Li N., et al. Efficacy and safety of glecaprevir/pibrentasvir for chronic hepatitis C virus genotypes 1-6 infection: a systematic review and meta-analysis. Int J Antimicrob Agents. 2019; 54 (6): 780-9. doi: 10.1016/j.ijantimicag.2019.07.005

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
Aleksandr V. Gorelov
Academician of the Russian Academy of Sciences, MD, Head of Infection Diseases and Epidemiology Department of the Scientific and Educational Institute of Clinical Medicine named after N.A. Semashko ofRussian University of Medicine, Ministry of Health of the Russian Federation, Professor of the Department of Childhood Diseases, Clinical Institute of Children's Health named after N.F. Filatov, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Deputy Director for Research, Central Research Institute of Epidemiology, Rospotrebnadzor (Moscow, Russian Federation)

Journals of «GEOTAR-Media»