Hepatitis C, Chronic
Conditions
Brief summary
This randomized, open-label, multi-center study will evaluate the sustained virological response, pharmacokinetics and safety of various combinations of danoprevir/ritonavir with Copegus plus RO5024048 and/or Pegasys in patients with chronic hepatitis C infection. Patients will be divided into 2 separate cohorts. Cohort A, previous partial responders, will be randomized to Groups 1-3 and cohort B, previous null responders, will be randomized to Groups 4-6. Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Groups 1 and 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Groups 3, 5 and 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.
Interventions
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, age 18 years and older * Presence of hepatitis C infection, genotype 1a or 1b * Documentation of previous treatment failure after receiving approved doses of peginterferon plus ribavirin for at least 12 weeks * Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to study start
Exclusion criteria
* Infection with any hepatitis C genotype or subtype other than genotype 1a or 1b * Patients with cirrhosis * Patients who were discontinued from previous peginterferon plus ribavirin therapy due to reasons other than insufficient therapeutic response * Co-infection with hepatitis B or human immunodeficiency virus (HIV) * History or evidence of chronic liver disease other than hepatitis C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained virological response (SVR) of danoprevir/ritonavir with RO5024048 and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment | 24 weeks |
| Sustained virological response (SVR) of danoprevir/ritonavir with Pegasys and Copegus in patients with previous partial response to peginterferon/ribavirin treatment | 24 weeks |
| Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment | 24 weeks |
| Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus followed by 24 weeks of Pegasys and Copegus treatment in patients with previous null response to peginterferon/ribavirin treatment | 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in danoprevir plasma concentration | 24 weeks |
| Safety (Incidence of adverse events) of danoprevir, RO5024048 and Copegus | 48 weeks |
| Hepatitis C virus drug resistance profile | 24 weeks |
| Change in RO5024048 plasma concentration | 24 weeks |
| Safety (Incidence of adverse events) of danoprevir, Pegasys and Copegus | 48 weeks |
| Safety (Incidence of adverse events) of danoprevir, RO5024048, Pegasys and Copegus | 72 weeks |
| Virological response over time | 48 weeks |
Countries
Australia, Austria, Brazil, Canada, France, Germany, Italy, Mexico, Poland, Puerto Rico, Spain, United Kingdom, United States
Outcome results
None listed