A Randomized, Double-blind, Multicenter, Dose and Duration Finding Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug (RO5024048) in Combination With Pegasys® and Ribavirin® (SOC) Versus SOC in Treatment-Naïve Patients With HCV Genotype 1 or 4 Infection
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 413
- Primary Endpoint
- Sustained virologic response: Percentage of patients with undetectable Hepatitis C RNA level
Study Overview
Brief Summary
This 6-arm study will assess the efficacy and safety of RO5024048 (R7128) in combination with the approved doses of Pegasys (180micrograms sc weekly) + Copegus (1000/1200mg po daily) (SOC), versus SOC in treatment-naive patients with chronic hepatitis C, genotype 1 and 4. The first 3 groups will receive 1) RO5024048 500mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks; 2)RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks; 3) RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients in these 3 groups who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks, and group 5 will receive SOC for 48 weeks. Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks. The anticipated time on study treatment is 6-12 months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients, 18-65 years of age
- •Chronic hepatitis C, genotype 1 or 4
- •Treatment-naive
Exclusion Criteria
- •No previous treatment with any interferon- or ribavirin-based therapy
- •Other forms of liver disease
- •HIV infection
Arms & Interventions
Group 3
RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Pegasys (Drug)
Group 5
Group 5 will receive SOC for 48 weeks
Intervention: Pegasys (Drug)
Group 1
RO5024048 500 mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Copegus (Drug)
Group 1
RO5024048 500 mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Pegasys (Drug)
Group 1
RO5024048 500 mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: RO5024048 (Drug)
Group 2
RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Copegus (Drug)
Group 2
RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Pegasys (Drug)
Group 2
RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: RO5024048 (Drug)
Group 3
RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: Copegus (Drug)
Group 3
RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.
Intervention: RO5024048 (Drug)
Group 4
Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks
Intervention: Copegus (Drug)
Group 4
Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks
Intervention: Pegasys (Drug)
Group 4
Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks
Intervention: RO5024048 (Drug)
Group 5
Group 5 will receive SOC for 48 weeks
Intervention: Copegus (Drug)
Group 6
Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks.
Intervention: Copegus (Drug)
Group 6
Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks.
Intervention: Pegasys (Drug)
Group 6
Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks.
Intervention: RO5024048 (Drug)
Outcomes
Primary Outcomes
Sustained virologic response: Percentage of patients with undetectable Hepatitis C RNA level
Time Frame: 24 weeks after end of treatment
Secondary Outcomes
- Virologic response: Percentage of patients with undetectable Hepatitis C RNA level(12 weeks post-treatment)
- Relapse rate: Percentage of patients who achieved a virologic response at the end of treatment but had detectable Hepatitis C RNA level at the last assessment post treatment(72 weeks)
- Safety: Incidence of adverse events(72 weeks)