A Study of RO5024048 in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients With Chronic Hepatitis C Genotype 1 or 4

Study Overview
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Brief Summary
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This equally randomized (1:1), double-blind, parallel arm study will assess the safety and antiviral efficacy of RO5024048 added to standard Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin) therapy in patients with chronic hepatitis C genotype 1 or 4. Patients in arm A will receive RO5024048 (1000mg orally twice daily) for 24 weeks in addition to Pegasys (180 micrograms sc weekly) and Copegus (1000mg or 1200mg orally daily). Patients achieving a rapid virological response (RVR) at week 4, sustained through week 22, will stop all treatment at week 24; non-RVR patients will continue treatment with Pegasys and Copegus for another 24 weeks up to week 48. Patients in arm B will receive standard treatment with Pegasys (180 micrograms sc weekly) and Copegus (1000mg or 1200mg orally daily) for 48 weeks. Anticipated time on study treatment is up to 48 weeks. Target sample size is <200.

Official Title
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A Randomized, Double-blinded, Multicenter Study to Evaluate the Antiviral Efficacy and Safety of Adding the HCV Polymerase Inhibitor Prodrug (RO5024048) for 24 Weeks to the Currently Approved Combination of Pegasys® and Copegus® in Treatment-Naïve Patients With Chronic Hepatitis C Genotype 1 or 4

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: RO5024048
* Drug: Ribavirin [Copegus]
* Drug: peginterferon alfa-2a [Pegasys]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-70 years of age hepatitis C, genotype 1 or 4, of over 6 months duration treatment-naïve negative pregnancy test; female patients of childbearing age and male patients with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin Exclusion Criteria: pregnant or breast feeding females or male partners of pregnant females previous interferon or ribavirin based therapy or investigational anti-HCV agent systemic antiviral therapy with established or perceived activity against HCV </=3 months prior to first dose of study drug hepatitis A or B, or HIV infection history or evidence of medical condition associated with chronic liver disease other than HCV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: With RO5024048<br>Patients in arm A will receive RO5024048 (1000mg orally twice daily) for 24 weeks in addition to Pegasys (180 micrograms sc weekly) and Copegus (1000mg or 1200mg orally daily). | Drug: RO5024048<br>* 1000mg bid po, 24 weeks<br>Drug: Ribavirin [Copegus]<br>* 1000mg or 1200mg po daily<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180mcg sc weekly<br>|
| Active Comparator: Arm B: Standard treatment<br>Patients in arm B will receive standard treatment with Pegasys (180 micrograms sc weekly) and Copegus (1000mg or 1200mg orally daily) for 48 weeks. | Drug: Ribavirin [Copegus]<br>* 1000mg or 1200mg po daily<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180mcg sc weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response (undetectable HCV DNA as measured by Roche COBAS TaqMan HCV test) |  | 24 weeks after last treatment dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic response over time |  | weeks 4, 12, 24, 36, 48 and 60 | 
| Pharmacokinetics of RO4995855 when RO5024048 is administered with peginterferon alfa-2a and ribavirin |  | week 12 and 24 | 
| Resistance profile of RO5024048 |  | weeks 1-24 |