A Study of Danoprevir Boosted With Low Dose Ritonavir in Combination With Pegasys and Copegus in Treatment-Naive Patients With Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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This randomized, open-label, active-controlled, parallel-group study will evaluate the sustained virological response of danoprevir boosted with low dose ritonavir in combination with Pegasys (peginterferon alfa-2a) and Copegus versus Pegasys and Copegus alone in treatment-naive patients with chronic Hepatitis C.

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Copegus
* Drug: Danoprevir
* Drug: Danoprevir
* Drug: Danoprevir
* Drug: Pegasys
* Drug: Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults patients, >/=18 years of age Chronic Hepatitis C, Genotype 1 and 4 HCV RNA >/=50,000 IU/mL treatment-naive Exclusion Criteria: Patients with cirrhosis or incomplete/transition to cirrhosis Patients with other forms of liver disease, HIV infection, hepatocellular carcinoma or severe cardiac disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Danoprevir 200 mg twice a day (BID) + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks | Drug: Copegus<br>* Copegus 1000 mg or 1200 mg po daily for 24 weeks.<br>Drug: Danoprevir<br>* Danoprevir 200 mg BID<br>Drug: Pegasys<br>* Pegasys 180 microgram sc qw<br>Drug: Ritonavir<br>* Ritonavir 100 mg<br>|
| Experimental: Group B<br>Danoprevir 100 mg BID + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks | Drug: Copegus<br>* Copegus 1000 mg or 1200 mg po daily for 24 weeks.<br>Drug: Danoprevir<br>* Danoprevir 100 mg BID<br>Drug: Pegasys<br>* Pegasys 180 microgram sc qw<br>Drug: Ritonavir<br>* Ritonavir 100 mg<br>|
| Experimental: Group C<br>Danoprevir 50 mg BID + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks | Drug: Copegus<br>* Copegus 1000 mg or 1200 mg po daily for 24 weeks.<br>Drug: Danoprevir<br>* Danoprevir 50 mg BID<br>Drug: Pegasys<br>* Pegasys 180 microgram sc qw<br>Drug: Ritonavir<br>* Ritonavir 100 mg<br>|
| Experimental: Group D<br>Danoprevir 100 mg BID + ritonavir 100 mg + Pegasys 180 μg sc qw + Copegus 1000 mg or 1200 mg po daily for 12 weeks or 24 weeks | Drug: Copegus<br>* Copegus 1000 mg or 1200 mg po daily for 24 weeks.<br>Drug: Danoprevir<br>* Danoprevir 100 mg BID<br>Drug: Pegasys<br>* Pegasys 180 microgram sc qw<br>Drug: Ritonavir<br>* Ritonavir 100 mg<br>|
| Active Comparator: Group E<br>Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 48 weeks | Drug: Copegus<br>* Copegus 1000 mg or 1200 mg po daily for 24 weeks.<br>Drug: Pegasys<br>* Pegasys 180 microgram sc qw<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response (HCV RNA measured by Roche COBAS TaqMan HCV test) |  | 24 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | from baseline up to 72 weeks | 
| Evaluation of relapse rate |  | up to 24 weeks after end of treatment | 
| Characterization of resistance profile (HCV RNA sequencing and/or phenotypic analyses) |  | from baseline up to 72 weeks | 
| Virological response at scheduled visits over time (HCV RNA measured by Roche COBAS TaqMan HCV test) |  | From baseline up to 72 weeks | 
| Evaluation of virological breakthrough (viral load rebound) rate |  | up to 72 weeks | 
| Evaluation of pharmacokinetics (serum concentrations assessed by validated methods) |  | up to 72 weeks |