A Study of Ritonavir-Boosted Danoprevir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients of Asian Origin With Chronic Hepatitis C Genotype 1 With or Without Cirrhosis

Study Overview
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Brief Summary
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This Phase II, open-label, parallel-arm study will evaluate the safety, tolerability, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) in treatment-naïve patients of Asian origin with chronic hepatitis C genotype 1. Patients will receive danoprevir 125 mg plus ritonavir 100 mg as fixed dose tablet orally twice daily in combination with weekly Pegasys 180 mcg subcutaneously and Copegus 1000-1200 mg orally daily in divided doses. Treatment duration is 12 weeks in patients without cirrhosis and 24 weeks in patients with compensated cirrhosis.

Official Title
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STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTIVIRAL ACTIVITY OF RITONAVIR-BOOSTED DANOPREVIR IN COMBINATION WITH PEGINTERFERON ALFA-2A PLUS RIBAVIRIN IN TREATMENT-NAÏVE PATIENTS OF ASIAN ORIGIN WHO HAVE CHRONIC HEPATITIS C GENOTYPE 1 WITH OR WITHOUT COMPENSATED CIRRHOSIS

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: danoprevir + ritonavir
* Drug: danoprevir + ritonavir
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: ribavirin [Copegus]
* Drug: ribavirin [Copegus]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients of East Asian or Southeast Asian origin, >/= 18 years of age Presence of chronic genotype 1 hepatitis C infection Treatment-naïve Exclusion Criteria: History or presence of decompensated liver disease Presence or history of non-hepatitis C chronic liver disease Positive for hepatitis B or HIV infection

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: with cirrhosis<br> | Drug: danoprevir + ritonavir<br>* 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 24 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 24 weeks<br>Drug: ribavirin [Copegus]<br>* 1000-1200 mg orally daily in divided doses, 24 weeks<br>|
| Experimental: without cirrhosis<br> | Drug: danoprevir + ritonavir<br>* 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 12 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly, 12 weeks<br>Drug: ribavirin [Copegus]<br>* 1000-1200 mg orally daily in divided doses, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 1.5 years | 
| Pharmacokinetics: Area under the concentration-time curve (AUC) for danoprevir/ritonavir |  | up to 14 days | 
| Antiviral activity: Change in HCV RNA levels, measured using Roche COBAS TaqMan HCV Test v2.0 for High Pure System |  | from baseline to Week 36/48 | 
| Antiviral activity: Proportion of patients with unquantifiable/undetectable HCV RNA during the study |  | approximately 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of viral resistance to danoprevir |  | approximately 1.5 years | 
| Rapid virological response (RVR): Proportion of patients with undetectable HCV RNA at Week 4 |  | approximately 1.5 years | 
| Complete early virological response (cEVR): Proportion of patients with undetectable HCV RNA at Week 12 |  | approximately 1.5 years | 
| Sustained virological response 12 weeks after end of treatment (SVR-12), defined as unquantifiable HCV RNA 8-20 weeks after the last day of study drug administration |  | approximately 1.5 years | 
| Sustained virological response 24 weeks after end of treatment (SVR-24), defined as unquantifiable HCV RNA > 20 weeks after the last day of study drug administration |  | approximately 1.5 years | 
| SVR measured as HCV RNA log10 IU/mL change from baseline to Week 12 |  | approximately 1.5 years |