Hepatitis C, Chronic
Conditions
Brief summary
This multicenter, randomized, double-blind, parallel group study will evaluate the safety and efficacy of the combination RO5024048 and ritonavir-boosted danoprevir with and without Copegus (ribavirin) in patients with chronic hepatitis C genotype 1. In arm A and B, interferon treatment-naïve patients will receive 1000 mg RO5024048 orally twice daily and 100 mg danoprevir with 100 mg ritonavir orally twice daily plus either Copegus (1000 mg or 1200 mg orally daily) or placebo for 12 weeks. Depending on viral response and treatment arm patients will be re-randomized to continue assigned treatment for additional 12 weeks or stop all treatment. The anticipated time on study treatment is up to 24 weeks plus a 24-week follow-up. As of 29. September 2011, Arm B patients (placebo-containing arm) will be offered, in conjunction with the current treatment, Pegasys (peginterferon alfa-2a) 180 mcg subcutaneously weekly plus Copegus 1000mg or 1200 mg orally daily for 24 weeks, with a 24-week follow-up.
Interventions
DRUGCopegus placebo
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
DRUGRO5024048
1000 mg bid orally, up to 24 weeks
DRUGdanoprevir
100 mg bid orally, up to 24 weeks
DRUGpeginterferon alfa-2a [Pegasys]
180 mcg sc weekly, 24 weeks
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
DRUGritonavir
100 mg bid orally, up to 24 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient, \>/= 18 years of age * Chronic Hepatitis C of \>/= 6 months duration at screening * HCV genotype 1 and quantifiable HCV RNA at screening (Roche COBAS TaqMan HCV test) * Naïve for treatment with interferon (pegylated or non-pegylated) * Body Mass Index (BMI) 18-35 inclusive, minimum weight 45 kg * Females of child-bearing potential and males with female partners of childbearing potential must use 2 forms of effective non-hormonal contraception
Exclusion criteria
* Pregnant or lactating women and males with female partners who are pregnant or lactating * Decompensated liver disease or impaired liver function * Cirrhosis or incomplete/transition to cirrhosis * Non-hepatitis C chronic liver disease * Hepatitis B or HIV infection * History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin * History of pre-existing renal disease (except for nephrolithiasis) or severe cardiac disease * History of drug or alcohol abuse within the last year or alcohol consumption of \> 2 units per day; cannabinoid use is excepted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test | 24 weeks after end of treatment |
| Safety: Incidence of adverse events | 1.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) | 1.5 years |
| Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin | up to 24 weeks |
| Virological response (HCV RNA measured by Roche COBAS Taqman HCV test) | up to 48 weeks |
| Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) | 1.5 years |
| Quality of life: SF-36 questionnaire, Fatigue Severity Scale | up to 36 weeks |
| Viral resistance: HCV RNA sequencing and phenotypic analyses | up to 48 weeks |
| Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) | 1.5 years |
Countries
France, Germany, New Zealand, United States
Outcome results
None listed