A Phase II, Randomized, Double-Blind, Multicenter, Parallel Group Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug RO5024048 in Combination With Boceprevir and Pegasys®/Copegus® in Patients With Chronic Hepatitis C Genotype 1 Virus Infection Who Were Prior Null Responders to Treatment With Pegylated Interferon/Ribavirin
Overview
- Phase
- Phase 2
- Intervention
- Copegus
- Conditions
- Hepatitis C, Chronic
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 58
- Primary Endpoint
- Sustained virological response 12 weeks after treatment (SVR-12)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This randomized, double-blind, multi-center, placebo-controlled, parallel-group study will evaluate the sustained virologic response and the safety of mericitabine (RO5024048) in combination with boceprevir and Pegasys/Copegus in patients with chronic hepatitis C infection. The anticipated time on study treatment is up to 48 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult patients, \>/=18 years of age
- •Chronic hepatitis C infection for at least 6 months duration
- •Hepatitis C genotype 1a or 1b
- •Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to enrollment in this study
- •Patient showed a previous null response to therapy as defined by \< 2 log10 IU/mL decrease in viral titer after at least 12 weeks of treatment with PEG-IFN/RBV
Exclusion Criteria
- •Hepatitis C infection with a genotype other than genotype 1a or 1b
- •Body mass index \<18 or \>/=36
- •Hepatitis A, hepatitis B, or HIV infection
- •Herbal remedies \</=1 month prior to the first dose of study drug
Arms & Interventions
Treatment Arm A
24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Copegus
Treatment Arm A
24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Pegasys
Treatment Arm A
24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: boceprevir
Treatment Arm A
24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: mericitabine
Treatment Arm B
24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Copegus
Treatment Arm B
24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Pegasys
Treatment Arm B
24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: boceprevir
Treatment Arm B
24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: mericitabine
Treatment Arm C (Control)
4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Copegus
Treatment Arm C (Control)
4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: Pegasys
Treatment Arm C (Control)
4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: mericitabine placebo
Treatment Arm C (Control)
4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: boceprevir placebo
Treatment Arm C (Control)
4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.
Intervention: boceprevir
Outcomes
Primary Outcomes
Sustained virological response 12 weeks after treatment (SVR-12)
Time Frame: up to 60 weeks
Secondary Outcomes
- Virologic response over time(60 weeks)
- Proportion of patients who develop treatment resistance(60 weeks)
- Sustained virological response 4 weeks after treatment(up to 52 weeks)
- Safety (incidence of adverse events)(60 weeks)
- Pharmacokinetics: trough concentration of RO4995855(Day 1 and Week 8)
- Pharmacokinetics: trough concentration of RO5012433(Day 1 and Week 8)
- Pharmacokinetics: trough concentration of boceprevir(Day 1 and Week 8)