A Study of Ritonavir-Boosted Danoprevir (RO5190591) in Combination With Pegasys and Ribavirin in Patients With Chronic Hepatitis C Genotype 1

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the efficacy, safety and tolerability of danoprevir (RO5190591) plus ritonavir as compared to danoprevir alone or placebo plus ritonavir in patients with chronic hepatitis C genotype 1 receiving Pegasys (peginterferon alfa-2a) and ribavirin. Patients in cohorts will be randomized to receive either oral doses of danoprevir, or danoprevir plus ritonavir, or placebo plus ritonavir. All patients will receive Pegasys (180mcg sc once weekly) plus ribavirin (1000-1200mg/day po), with the option to continue this treatment after completion of study drug treatment. Anticipated time on study treatment is up to 12 weeks.

Official Title
-----------------
A Multiple-Dose Study To Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted RO5190591 in Combination With Peginterferon Alfa-2a Plus Ribavirin in Patients With Chronic Hepatitis C Genotype 1

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

Intervention / Treatment
-----------------
* Drug: danoprevir
* Drug: peginterferon alfa-2a [Pegasys]
* Drug: placebo
* Drug: ribavirin
* Drug: ritonavir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults, 18-65 years of age Chronic hepatitis C genotype 1 HCV treatment naïve, or without sustained virologic response on prior PEG-INF/RBV treatment Body mass index (BMI) 18 - 35 kg/m2, inclusive; minimum weight 45 kg Exclusion Criteria: Liver cirrhosis Decompensated liver disease or impaired liver function Medical condition associated with chronic liver disease other than chronic hepatitis C Positive for hepatitis B or HIV infection at screening History of alcohol consumption exceeding 2 standard drinks per day when averaged over the course of a given week

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: danoprevir<br>* oral doses<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc once weekly<br>Drug: ribavirin<br>* 1000-1200mg/day po<br>|
| Experimental: B<br> | Drug: danoprevir<br>* oral doses<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc once weekly<br>Drug: ribavirin<br>* 1000-1200mg/day po<br>Drug: ritonavir<br>* oral doses<br>|
| Placebo Comparator: C<br> | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc once weekly<br>Drug: placebo<br>* oral doses<br>Drug: ribavirin<br>* 1000-1200mg/day po<br>Drug: ritonavir<br>* oral doses<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Adverse events, ECG, laboratory parameters |  | approximately 3 years | 
| Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2 |  | Days 3-9 | 
| Antiviral activity: HCV RNA (COBAS Taqman HCV Test) |  | from baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral resistance development |  | from baseline to Day 17 | 
| Effects on cytochrome P450(CYP)2C9 and 3A isozymes |  | from baseline to Day 17 | 
| Virological response in prior null-responders |  | from baseline to week 72 | 
| Comparison of pharmacokinetics and antiviral activity between treatment-naïve patients and prior null-responders to standard of care treatment |  | approximately 3 years |