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).

scholarly journals An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTime HCV RNA Assay

2015 ◽  
Vol 53 (4) ◽  
pp. 1264-1269 ◽  
Author(s):  
Christoph Sarrazin ◽  
Inge Dierynck ◽  
Gavin Cloherty ◽  
Anne Ghys ◽  
Katrien Janssen ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Similar Proportion ◽  
Hcv Rna ◽  
Pure System ◽  
Treatment Naïve ◽  
Total Therapy

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.)

scholarly journals Efficacy and Safety of Danoprevir-Ritonavir plus Peginterferon Alfa-2a–Ribavirin in Hepatitis C Virus Genotype 1 Prior Null Responders

2013 ◽  
Vol 58 (2) ◽  
pp. 1136-1145 ◽  
Author(s):  
Edward J. Gane ◽  
Régine Rouzier ◽  
Alicja Wiercinska-Drapalo ◽  
Dominique G. Larrey ◽  
Peter N. Morcos ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Hcv Rna ◽  
Efficacy And Safety ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Peginterferon Alfa

ABSTRACTDanoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a–ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a–ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a–ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a–ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had anIL28Bnon-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a–ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered atClinicalTrials.govunder registration no. NCT01185860.)

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 Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir Regimen in Haemodialysis Patients With Hepatitis C Virus Infection

2020 ◽  
Vol 39 (1) ◽  
pp. 23-27
Author(s):  
Antonija Verhaz ◽  
Tatjana Roganović ◽  
Ljiljana Pašić ◽  
Olja Čuković ◽  
Tanja Macanović-Kostić
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Concomitant Medication ◽  
Demographic Data ◽  
Virologic Response ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Stage Renal Disease

Background: Hepatitis C virus (HCV) infection is common among patients on haemodialysis (HD) therapy and is an important cause of morbidity and mortality. In patients with chronic kidney disease (CKD), the risks for negative outcomes are significantly higher in HCV-infected patients than in those without HCV infection, including progression to cirrhosis, hepatocellular carcinoma and liver-related mortality. Ombitasvir (OBV), paritaprevir (PTV), ritonavir (r), and dasabuvir (DSV) are all hepatically metabolized and, therefore, require no dose adjustment in patients with any degree of renal impairment. Aims: We studied the safety and efficacy of OBV/PTV/r + DSV in a small group of HCV infected patients on haemodialysis therapy. Methods: Treatment course with ombitasvir/paritaprevir/ritonavir and dasabuvir; (3-DAA regimen of OBV/PTV/r+DSV±RBV) was analysed. Pre-treatment evaluation of HCV infection included HCV RNA, genotype, and liver fibrosis assed by transient fibroelastography (FibroScan). The stage 5 CKD was defined as an eGFR of &lt;15 mL/min/1.73 m2, respectively; those on haemodialysis were considered to have stage 5 CKD or end-stage renal disease (ESRD). Demographic data and concomitant medication were retrieved from patients’ records. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Among 7 treated patients, 6 were male and 1 female, all were infected with genotype 1 (5 GT1b, 2 GT1a). Patient had compensated liver cirrhosis and six patients did not have liver cirrhosis, none were liver transplant recipients. All of seven patients completed 12 weeks of treatment and achieved SVR12. Concomitant medication had to be modified with the treatment initiation in 5 out of 7 patients. One of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, diarrhoea. Adverse events were primarily mild, and no patient discontinued treatment due to an AE. Conclusions: Treatment with OBV/PTV/r +DSV ± RBV was well-tolerated and resulted in high rates of SVR12 (100%) for patients with HCV GT1b/1a on haemodialysis.

scholarly journals Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
John A. Howe ◽  
Jianmin Long ◽  
Stuart Black ◽  
Robert Chase ◽  
Patricia McMonagle ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Failure ◽  
Virologic Response ◽  
Phase Iii ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Virus Genotype ◽  
The Impact

Abstract Background.  We analyzed the impact of pretreatment variants conferring boceprevir-resistance on sustained virologic response (SVR) rates achieved with boceprevir plus peginterferon-α/ribavirin (P/R) for hepatitis C virus (HCV)-genotype-1 infection. Methods.  NS3-protease-polymorphisms emerging coincident with virologic failure on boceprevir/P/R regimens were identified as resistance-associated variants (RAVs). Baseline samples pooled from 6 phase II or phase III clinical trials were analyzed for RAVs by population sequencing. Interferon (IFN)-responsiveness was predefined as &gt;1 log reduction in HCV-RNA level during the initial 4-week lead-in treatment with P/R before boceprevir was added. The effective boceprevir-concentration inhibiting RAV growth by 50% (EC50) was determined using a replicon assay relative to the wild-type referent. Results.  Sequencing was performed in 2241 of 2353 patients (95.2%) treated with boceprevir. At baseline, RAVs were detected in 178 patients (7.9%), including 153 of 1498 genotype-1a infections (10.2%) and 25 of 742 genotype-1b infections (3.4%) (relative risk, 3.03; 95% confidence interval [CI], [2.01, 4.58]). For IFN-responders, SVR24 (SVR assessed 24 weeks after discontinuation of all study medications) rates were 78% and 76% with or without RAVs detected at baseline, respectively. For the 510 poor IFN-responders, SVR24 rates were 8 of 36 subjects (22.2% [11.7%, 38.1%]) when baseline RAVs were detected vs 174 of 474 subjects (36.7% [32.5%, 41.1%]) when baseline RAVs were not detected (relative likelihood of SVR24 [95% CI], 0.61 [0.32, 1.05]). Sustained virologic response was achieved in 7 of 8 (87.5%) IFN-nonresponders with baseline variants exhibiting ≤2-fold increased EC50 for boceprevir in a replicon assay, whereas only 1 of 15 (7%) IFN-nonresponders with baseline RAVs associated with ≥3-fold increased EC50 achieved SVR. Conclusions.  Baseline protease-variants appear to negatively impact SVR rates for boceprevir/P/R regimens only when associated with decreased boceprevir susceptibility in vitro after a poor IFN-response during the lead-in period.

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