Hepatitis C, Chronic
Conditions
Brief summary
This open-label, parallel cohort study will evaluate the safety, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients, and with RO5024048 added to the combination treatment in prior null responder patients with chronic hepatitis C genotype 1 or 4 and compensated cirrhosis. All patients will receive danoprevir 100 mg orally twice daily (bid) , ritonavir 100 mg orally bid, Pegasys 180 mcg subcutaneously weekly and ribavirin 1000-1200 mg/kg/day orally. Prior non-responders will receive RO5024048 1000 mg orally bid additionally. Anticipated time on study treatment is 24 weeks.
Interventions
DRUGRO5024048
1000 mg orally bid, 24 weeks
DRUGdanoprevir
100 mg orally bid, 24 weeks
DRUGpeginterferon alfa-2a [Pegasys]
180 mcg weekly, 24 weeks
DRUGribavirin
1000-1200 mg/kg/day orally in two divided doses, 24 weeks
DRUGritonavir
100 mg orally bid, 24 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, 18 to 65 years of age inclusive * Chronic hepatitis C, genotype 1 or 4 * Cohort 1: Treatment-naïve for hepatitis C * Cohort 2: Prior null responder to treatment with approved doses of pegylated interferon plus ribavirin * Liver biopsy confirming cirrhosis * Compensated cirrhosis (Child-Pugh A)
Exclusion criteria
* Pregnant or lactating women or male partners of women who are pregnant * History or presence of decompensated liver disease (ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices) * Cohort 2: Patients who discontinued previous pegylated interferon plus ribavirin treatment due to reasons other than null response * History of clinically significant cardiovascular or cerebrovascular disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Incidence of adverse events | 48 weeks |
| Pharmacokinetics (PK): Area under the concentration-time curve (AUC) | Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24 |
| Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test | 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Emergence of viral resistance: HCV RNA gene sequence variations | From baseline to Week 48 |
| Virologic response: HCV RNA levels | approximately 1 year |
Countries
Australia, Canada, France, New Zealand, Poland, Slovakia, United States
Outcome results
None listed