A Study of Hepatitis C Virus (HCV) Polymerase Inhibitor Pro-Drug in Combination With PEGASYS With or Without COPEGUS in Patients With Chronic Hepatitis C (CHC) Genotype 1 Infection.

Study Overview
=================
Brief Summary
-----------------
This 4 arm study will compare the safety and tolerability of HCV polymerase inhibitor pro-drug in combination with PEGASYS +/- COPEGUS with the standard of care therapy of PEGASYS + COPEGUS, in treatment-naive patients with CHC, genotype 1. Patients will be randomized to receive 1500mg or 3000mg po bid of HCV polymerase inhibitor pro-drug + PEGASYS, 1500mg of HCV polymerase inhibitor pro-drug + PEGASYS + COPEGUS or PEGASYS + COPEGUS for 4 weeks. All patients who receive at least one dose of study medication will receive open label PEGASYS + Copegus for an additional 44 weeks after the 4 week experimental period. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
-----------------
A Randomized, Double-blind Study to Evaluate the Safety and Tolerability of the HCV Polymerase Inhibitor Pro-drug in Combination With Pegasys, With or Without Copegus, Versus Pegasys Plus Copegus, in Treatment-naïve Patients With Chronic Hepatitis C, Genotype 1

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: Copegus
* Drug: PEGASYS
* Drug: RO5024048 1500mg
* Drug: RO5024048 3000mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patients, 18-65 years of age; CHC without liver cirrhosis or incomplete/transition to liver cirrhosis, genotype 1; chronic liver disease consistent with CHC. 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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PEGASYS with COPEGUS<br> | Drug: Copegus<br>* 1000/1200mg po daily for 4 weeks<br>Drug: PEGASYS<br>* 180 micrograms sc weekly for 4 weeks<br>|
| Experimental: RO5024048 1500mg in combination with PEGASYS<br> | Drug: PEGASYS<br>* 180 micrograms sc weekly for 4 weeks<br>Drug: RO5024048 1500mg<br>* 1500mg po bid for 4 weeks<br>|
| Experimental: RO5024048 3000mg in combination with PEGASYS<br> | Drug: PEGASYS<br>* 180 micrograms sc weekly for 4 weeks<br>Drug: RO5024048 3000mg<br>* 3000mg po bid for 4 weeks<br>|
| Experimental: RO5024048 in combination with PEGASYS and COPEGUS<br> | Drug: Copegus<br>* 1000/1200mg po daily for 4 weeks<br>Drug: PEGASYS<br>* 180 micrograms sc weekly for 4 weeks<br>Drug: RO5024048 1500mg<br>* 1500mg po bid for 4 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) and laboratory parameters. |  | Week 4, 8 and Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of HCV polymerase inhibitor |  | Week 4 and 8 | 
| Antiviral activity |  | Week 4, 8 and Week 72 |