A Study of RO5024048 in Combination With Pegasys and Copegus in Treatment-Naive Patients With Chronic Hepatitis C, Genotype 1 or 4

Study Overview
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Brief Summary
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This 6-arm study will assess the efficacy and safety of RO5024048 (R7128) in combination with the approved doses of Pegasys (180micrograms sc weekly) + Copegus (1000/1200mg po daily) (SOC), versus SOC in treatment-naive patients with chronic hepatitis C, genotype 1 and 4. The first 3 groups will receive 1) RO5024048 500mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks; 2)RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks; 3) RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients in these 3 groups who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks, and group 5 will receive SOC for 48 weeks. Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks. The anticipated time on study treatment is 6-12 months.

Official Title
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A Randomized, Double-blind, Multicenter, Dose and Duration Finding Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug (RO5024048) in Combination With Pegasys® and Ribavirin® (SOC) Versus SOC in Treatment-Naïve Patients With HCV Genotype 1 or 4 Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Copegus
* Drug: Copegus
* Drug: Pegasys
* Drug: Pegasys
* Drug: RO5024048
* Drug: RO5024048
* Drug: RO5024048
* Drug: RO5024048


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 or 4 Treatment-naive Exclusion Criteria: No previous treatment with any interferon- or ribavirin-based therapy Other forms of liver disease HIV 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>RO5024048 500 mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. | Drug: Copegus<br>* 1000/1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5024048<br>* 500mg bid for 12 weeks<br>|
| Experimental: Group 2<br>RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. | Drug: Copegus<br>* 1000/1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5024048<br>* 1000mg bid for 8 weeks<br>|
| Experimental: Group 3<br>RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. | Drug: Copegus<br>* 1000/1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5024048<br>* 1000mg bid for 12 weeks<br>|
| Experimental: Group 4<br>Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks | Drug: Copegus<br>* 1000/1200mg po daily for 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 48 weeks<br>Drug: RO5024048<br>* 1000mg bid for 12 weeks<br>|
| Active Comparator: Group 5<br>Group 5 will receive SOC for 48 weeks | Drug: Copegus<br>* 1000/1200mg po daily for 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 48 weeks<br>|
| Experimental: Group 6<br>Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks. | Drug: Copegus<br>* 1000/1200mg po daily for 48 weeks<br>Drug: Pegasys<br>* 180 micrograms sc weekly for 48 weeks<br>Drug: RO5024048<br>* 1000mg bid for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response: Percentage of patients with undetectable Hepatitis C RNA level |  | 24 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic response: Percentage of patients with undetectable Hepatitis C RNA level |  | 60 Weeks | 
| Virologic response: Percentage of patients with undetectable Hepatitis C RNA level |  | 12 weeks post-treatment | 
| Relapse rate: Percentage of patients who achieved a virologic response at the end of treatment but had detectable Hepatitis C RNA level at the last assessment post treatment |  | 72 weeks | 
| Safety: Incidence of adverse events |  | 72 weeks |