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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01185860

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

14.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: danoprevir Drug: peginterferon alfa-2a [Pegasys] Drug: placebo Drug: ribavirin Drug: ritonavir	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: A

Drug: danoprevir

oral doses

Drug: peginterferon alfa-2a [Pegasys]

180 mcg sc once weekly

Drug: ribavirin

1000-1200mg/day po

Experimental: B

Drug: danoprevir

oral doses

Drug: peginterferon alfa-2a [Pegasys]

180 mcg sc once weekly

Drug: ribavirin

1000-1200mg/day po

Drug: ritonavir

oral doses

Placebo Comparator: C

Drug: peginterferon alfa-2a [Pegasys]

180 mcg sc once weekly

Drug: placebo

oral doses

Drug: ribavirin

1000-1200mg/day po

Drug: ritonavir

oral doses

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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