A Study of Hepatitis C Virus (HCV) Polymerase Inhibitor Pro-Drug in Combination With PEGASYS Plus COPEGUS Compared With PEGASYS Plus COPEGUS in Patients With Chronic Hepatitis C Genotype 1 Infection.

Study Overview
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Brief Summary
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This 7 arm study will determine the optimal treatment combination, based on efficacy and safety. Patients with chronic hepatitis C (CHC), genotype 1, will be randomized to one of 7 treatment groups. Groups 1, 2, 4, 5 and 6 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (at doses of 500, 1000 or 1500mg po bid) plus PEGASYS (90 or 180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). Group 3 will receive HCV polymerase inhibitor pro-drug 500mg po bid plus PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd for 24 weeks; after 24 weeks, those achieving a rapid virological response (RVR) will stop all medication, and non-RVR patients will remain on triple combination for an additional 24 weeks. Group 7 will receive standard of care (SOC) for 48 weeks. There will be a 24 week period of treatment-free follow-up for all treatment groups. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Double-blinded Study to Evaluate the Safety and Effect on Sustained Virological Response of HCV Polymerase Inhibitor Pro-drug in Combination With PEGASYS Plus Copegus, Compared With the Currently Approved Combination of PEGASYS Plus Copegus, in Treatment-naïve Patients With Chronic he

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Copegus
* Drug: Pegasys
* Drug: Pegasys
* Drug: RO4588161
* Drug: RO4588161
* Drug: RO4588161


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-65 years of age; chronic hepatitis C, genotype 1; chronic liver disease consistent with CHC; compensated liver disease. Exclusion Criteria: infection with any HCV genotype other than genotype 1; previous treatment for CHC; medical condition associated with chronic liver disease other than CHC; HIV, hepatitis A, hepatitis B infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Group 1<br>Group 1 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 1000mg po bid for 24 weeks<br>|
| Experimental: Group 2<br>Group 2 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 500mg po bid for 24 weeks<br>|
| Experimental: Group 3<br>Group 3 will receive HCV polymerase inhibitor pro-drug 500mg po bid plus PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd for 24 weeks; after 24 weeks, those achieving a rapid virological response (RVR) will stop all medication, and non-RVR patients will remain on triple combination for an additional 24 weeks. | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 500mg po bid for 24 weeks<br>|
| Experimental: Group 4<br>Group 4 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 90 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 1500mg po bid for 24 weeks<br>|
| Experimental: Group 5<br>Group 5 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 90 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 1000mg po bid for 24 weeks<br>|
| Experimental: Group 6<br>Group 6 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 90 micrograms sc weekly for 24 weeks<br>Drug: RO4588161<br>* 500mg po bid for 24 weeks<br>|
| Active Comparator: Group 7<br>Standard of care (SOC) | Drug: Copegus<br>* 1000/1200mg po daily for 24 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response (SVR) |  | 24 weeks post treatment end (ie weeks 48 or 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response over time |  | Throughout study | 
| SVR |  | 12 weeks post treatment end (ie weeks 36 or 60) | 
| Relapse rate |  | End of treatment (ie weeks 24 or 48) | 
| Adverse events (AEs), laboratory parameters. |  | Throughout treatment |