SCH 503034, a Novel Hepatitis C Virus Protease Inhibitor, Plus Pegylated Interferon α-2b for Genotype 1 Nonresponders

2007 ◽  
Vol 132 (4) ◽  
pp. 1270-1278 ◽  
Author(s):  
Christoph Sarrazin ◽  
Regine Rouzier ◽  
Frank Wagner ◽  
Nicole Forestier ◽  
Dominique Larrey ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitor ◽  
Pegylated Interferon ◽  
Interferon Α ◽  
Genotype 1

scholarly journals SILEN-C3, a Phase 2 Randomized Trial with Faldaprevir plus Pegylated Interferon α-2a and Ribavirin in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients

2014 ◽  
Vol 58 (6) ◽  
pp. 3429-3436 ◽  
Author(s):  
Douglas Dieterich ◽  
Tarik Asselah ◽  
Dominique Guyader ◽  
Thomas Berg ◽  
Marcus Schuchmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Interferon Α ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Once Daily ◽  
Treatment Naïve

ABSTRACTFaldaprevir is an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor which, when administered for 24 weeks in combination with pegylated interferon α-2a and ribavirin (PegIFN/RBV) in treatment-naive patients in a prior study (SILEN-C1; M. S. Sulkowski et al., Hepatology 57:2143–2154, 2013, doi:10.1002/hep.26276), achieved sustained virologic response (SVR) rates of 72 to 84%. The current randomized, open-label, parallel-group study compared the efficacy and safety of 12 versus 24 weeks of 120 mg faldaprevir administered once daily, combined with 24 or 48 weeks of PegIFN/RBV, in 160 treatment-naive HCV genotype 1 patients. Patients with maintained rapid virologic response (HCV RNA of <25 IU/ml at week 4 and undetectable at weeks 8 and 12) stopped all treatment at week 24, otherwise they continued PegIFN/RBV to week 48. SVR was achieved by 67% and 74% of patients in the 12-week and 24-week groups, respectively. Virologic response rates were lower in the 12-week group from weeks 2 to 12, during which both groups received identical treatment. SVR rates were similar in both groups for patients achieving undetectable HCV RNA. Most adverse events were mild or moderate, and 6% of patients in each treatment group discontinued treatment due to adverse events. Once-daily faldaprevir at 120 mg for 12 or 24 weeks with PegIFN/RBV resulted in high SVR rates, and the regimen was well tolerated. Differences in the overall SVR rates between the 12-week and 24-week groups were not statistically significant and possibly were due toIL28Bgenotype imbalances;IL28Bgenotype was not tested, as its significance was not known at the time of the study. These results supported phase 3 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT00984620).

Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferon-α in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1

2010 ◽  
Vol 139 (4) ◽  
pp. 1257-1266 ◽  
Author(s):  
Stefan Zeuzem ◽  
Mark S. Sulkowski ◽  
Eric J. Lawitz ◽  
Vinod K. Rustgi ◽  
Maribel Rodriguez–Torres ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Randomized Trial ◽  
Chronic Hepatitis C ◽  
Pegylated Interferon ◽  
Interferon Α ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Chronic Hepatitis C Virus

scholarly journals Hepatitis C Drugs: The End of the Pegylated Interferon Era and the Emergence of All-Oral, Interferon-Free Antiviral Regimens: A Concise Review

2014 ◽  
Vol 28 (8) ◽  
pp. 445-451 ◽  
Author(s):  
Alan Hoi Lun Yau ◽  
Eric M Yoshida
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitor ◽  
Sustained Virological Response ◽  
Virological Response ◽  
Second Generation ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Replication Complex ◽  
Polymerase Inhibitor

Between 2001 and 2011, the standard of care for chronic hepatitis C virus (HCV) infection was a combination of pegylated interferon (PEGIFN) and ribavirin (RBV). In May 2011, boceprevir and telaprevir, two first-generation NS3/4A protease inhibitors, were approved in combination with PEG-IFN and RBV for 24 to 48 weeks in hepatitis C virus genotype 1 infections. In December 2013, simeprevir, a second-generation NS3/4A protease inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotype 1, while sofosbuvir, a NS5B nucleotide polymerase inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotypes 1 and 4, as well as with RBV alone for 12 weeks in genotype 2 and for 24 weeks in genotype 3. Sofosbuvir combined with simeprevir or an NS5A replication complex inhibitor (ledipasvir or daclatasvir) with or without RBV for 12 weeks in genotype 1 resulted in a sustained virological response >90%, irrespective of previous treatment history or presence of cirrhosis. Similarly impressive sustained virological response rates have been shown with ABT-450/r (ritonavir-boosted NS3/4A protease inhibitor)-based regimens in combination with other direct-acting antiviral agent(s) with or without RBV for 12 weeks in genotype 1. The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS5A replication complex inhibitor with or without RBV. Further research is needed to determine the role of resistance testing, clarify the optimal follow-up duration post-treatment, and evaluate the antiviral efficacy and safety in difficult-to-cure patient populations.

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

2016 ◽  
Vol 25 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Tim Zimmermann ◽  
Dietrich Hueppe ◽  
Stefan Mauss ◽  
Peter Buggisch ◽  
Heike Pfeiffer-Vornkahl ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Virological Response ◽  
Sustained Viral Response ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Pegylated Interferon Alpha ◽  
Viral Response

Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.    

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