Cargando…
Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2)
Hepatitis C virus (HCV)–infected patients with cirrhosis are historically a difficult‐to‐treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor)...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297873/ https://www.ncbi.nlm.nih.gov/pubmed/26704148 http://dx.doi.org/10.1002/hep.28422 |
_version_ | 1782505801325215744 |
---|---|
author | Lawitz, Eric Matusow, Gary DeJesus, Edwin Yoshida, Eric M. Felizarta, Franco Ghalib, Reem Godofsky, Eliot Herring, Robert W. Poleynard, Gary Sheikh, Aasim Tobias, Hillel Kugelmas, Marcelo Kalmeijer, Ronald Peeters, Monika Lenz, Oliver Fevery, Bart De La Rosa, Guy Scott, Jane Sinha, Rekha Witek, James |
author_facet | Lawitz, Eric Matusow, Gary DeJesus, Edwin Yoshida, Eric M. Felizarta, Franco Ghalib, Reem Godofsky, Eliot Herring, Robert W. Poleynard, Gary Sheikh, Aasim Tobias, Hillel Kugelmas, Marcelo Kalmeijer, Ronald Peeters, Monika Lenz, Oliver Fevery, Bart De La Rosa, Guy Scott, Jane Sinha, Rekha Witek, James |
author_sort | Lawitz, Eric |
collection | PubMed |
description | Hepatitis C virus (HCV)–infected patients with cirrhosis are historically a difficult‐to‐treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1–infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open‐label, single‐arm study (OPTIMIST‐2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1–infected treatment‐naive or treatment‐experienced patients with cirrhosis. Patients (aged 18‐70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient‐reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%‐91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment‐naive and treatment‐experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient‐reported outcomes improved from baseline to follow‐up week 12. Conclusion: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment‐naive and treatment‐experienced HCV GT1‐infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360‐369) |
format | Online Article Text |
id | pubmed-5297873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52978732017-02-22 Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) Lawitz, Eric Matusow, Gary DeJesus, Edwin Yoshida, Eric M. Felizarta, Franco Ghalib, Reem Godofsky, Eliot Herring, Robert W. Poleynard, Gary Sheikh, Aasim Tobias, Hillel Kugelmas, Marcelo Kalmeijer, Ronald Peeters, Monika Lenz, Oliver Fevery, Bart De La Rosa, Guy Scott, Jane Sinha, Rekha Witek, James Hepatology Viral Hepatitis Hepatitis C virus (HCV)–infected patients with cirrhosis are historically a difficult‐to‐treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1–infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open‐label, single‐arm study (OPTIMIST‐2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1–infected treatment‐naive or treatment‐experienced patients with cirrhosis. Patients (aged 18‐70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient‐reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%‐91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment‐naive and treatment‐experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient‐reported outcomes improved from baseline to follow‐up week 12. Conclusion: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment‐naive and treatment‐experienced HCV GT1‐infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360‐369) John Wiley and Sons Inc. 2016-02-19 2016-08 /pmc/articles/PMC5297873/ /pubmed/26704148 http://dx.doi.org/10.1002/hep.28422 Text en © 2015 by The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Viral Hepatitis Lawitz, Eric Matusow, Gary DeJesus, Edwin Yoshida, Eric M. Felizarta, Franco Ghalib, Reem Godofsky, Eliot Herring, Robert W. Poleynard, Gary Sheikh, Aasim Tobias, Hillel Kugelmas, Marcelo Kalmeijer, Ronald Peeters, Monika Lenz, Oliver Fevery, Bart De La Rosa, Guy Scott, Jane Sinha, Rekha Witek, James Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title | Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title_full | Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title_fullStr | Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title_full_unstemmed | Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title_short | Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2) |
title_sort | simeprevir plus sofosbuvir in patients with chronic hepatitis c virus genotype 1 infection and cirrhosis: a phase 3 study (optimist‐2) |
topic | Viral Hepatitis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297873/ https://www.ncbi.nlm.nih.gov/pubmed/26704148 http://dx.doi.org/10.1002/hep.28422 |
work_keys_str_mv | AT lawitzeric simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT matusowgary simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT dejesusedwin simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT yoshidaericm simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT felizartafranco simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT ghalibreem simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT godofskyeliot simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT herringrobertw simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT poleynardgary simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT sheikhaasim simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT tobiashillel simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT kugelmasmarcelo simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT kalmeijerronald simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT peetersmonika simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT lenzoliver simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT feverybart simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT delarosaguy simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT scottjane simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT sinharekha simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 AT witekjames simeprevirplussofosbuvirinpatientswithchronichepatitiscvirusgenotype1infectionandcirrhosisaphase3studyoptimist2 |