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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 59
- Primary Endpoint
- Safety and tolerability: Adverse events, ECG, laboratory parameters
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
A
Intervention: danoprevir (Drug)
A
Intervention: peginterferon alfa-2a [Pegasys] (Drug)
A
Intervention: ribavirin (Drug)
B
Intervention: danoprevir (Drug)
B
Intervention: peginterferon alfa-2a [Pegasys] (Drug)
B
Intervention: ribavirin (Drug)
B
Intervention: ritonavir (Drug)
C
Intervention: peginterferon alfa-2a [Pegasys] (Drug)
C
Intervention: placebo (Drug)
C
Intervention: ribavirin (Drug)
C
Intervention: ritonavir (Drug)
Outcomes
Primary Outcomes
Safety and tolerability: Adverse events, ECG, laboratory parameters
Time Frame: approximately 3 years
Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2
Time Frame: Days 3-9
Antiviral activity: HCV RNA (COBAS Taqman HCV Test)
Time Frame: from baseline to Day 28
Secondary Outcomes
- 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)