A Study of RO5190591 (Danoprevir) in Combination With Pegasys and Copegus in Treatment-Naive Patients With Chronic Hepatitis C Genotype 1 Virus Infection

Study Overview
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Brief Summary
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This 2 part study will evaluate the efficacy and safety of 12 and 24 weeks treatment with RO5190591 (danoprevir) in combination with Pegasys and Copegus, compared to Pegasys and Copegus alone, in treatment-naive patients with chronic hepatitis C genotype 1 virus infection.In Part 1 of the study, patients will be randomized to receive either 1) RO5190591 300mg po every 8 hours, 2) RO5190591 600mg po every 12 hours, 3) RO5190591 900mg po every 12 hours or 4) placebo, in combination with standard doses of Pegasys and Copegus. If the safety and virological response data from Part 1 of the study are supportive, in Part 2 patients will be randomized to receive either 1) RO5190591 300mg po every 8 hours or 600mg po every 12 hours or 900mg po every 12 hours or 2)placebo, in combination with standard doses of Pegasys and Copegus. The anticipated time on study treatment is 24-48 weeks, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Partially-blind Study on the Safety, Tolerability and Effect on Virological Response of Treatment With the HCV Protease Inhibitor RO5190591 in Combination With Pegasys and Copegus, Versus Pegasys and Copegus Alone, in Treatment-Naïve Patients With Hepatitis C Genotype 1 Virus Infectio

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Copegus
* Drug: Pegasys
* Drug: Placebo
* Drug: Placebo
* Drug: RO5190591 (Danoprevir)
* Drug: RO5190591 (Danoprevir)
* Drug: RO5190591 (Danoprevir)
* Drug: RO5190591 (Danoprevir)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; chronic hepatitis C, genotype 1; treatment-naive. Exclusion Criteria: liver cirrhosis and other forms of liver disease; HIV infection; hepatocellular cancer; 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part 1: Placebo<br>Placebo in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: Placebo<br>* po for 12 weeks<br>|
| Experimental: Part 1: RO5190591 300mg po<br>RO5190591 300mg po every 8 hours in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5190591 (Danoprevir)<br>* 300mg po q8h for 12 weeks<br>|
| Experimental: Part 1: RO5190591 600mg po<br>RO5190591 600mg po every 12 hours in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5190591 (Danoprevir)<br>* 600mg po q12h for 12 weeks<br>|
| Experimental: Part 1: RO5190591 900mg po<br>RO5190591 900mg po every 12 hours in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5190591 (Danoprevir)<br>* 900mg po q12h for 12 weeks<br>|
| Placebo Comparator: Part 2: Placebo<br>If the safety and virological response data from Part 1 of the study are supportive, in Part 2 patients will be randomized to receive placebo in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: Placebo<br>* po for 24 weeks<br>|
| Experimental: Part 2: RO5190591 300mg po<br>If the safety and virological response data from Part 1 of the study are supportive, in Part 2 patients will be randomized to receive RO5190591 300mg po every 8 hours or 600mg po every 12 hours or 900mg po every 12 hours in combination with standard doses of Pegasys and Copegus. | Drug: Copegus<br>* 1000 or 1200mg po daily for 24 or 48 weeks<br>Drug: Pegasys<br>* 180micrograms sc weekly for 24 or 48 weeks<br>Drug: RO5190591 (Danoprevir)<br>* 300mg po q8h or 600mg po q12h or 900po q12h 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 |  | 24 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response over time |  | At 2- to 6-weekly intervals throughout study; at end of treatment; 12 weeks post-treatment | 
| Adverse events; laboratory parameters |  | Throughout study, laboratory parameters every 2 to 6 weeks |