A Multi-center, Open-Labeled Exploratory Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 400 mg and Ribavirin for 12 Weeks With and Without Pegylated Interferon in Treatment-Naïve Patients With Chronic HCV Infection Genotype 2 or Genotype 3
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 292
- Locations
- 2
- Primary Endpoint
- Percentage of Participants Who Experienced Adverse Events
Study Overview
Brief Summary
This study is to assess the safety and tolerability of sofosbuvir (SOF) 400 mg with and without ribavirin (RBV) and/or with and without pegylated interferon alfa-2a (PEG) in subjects with genotype 1, 2 or 3 hepatitis C (HCV) infection.
Detailed Description
Part 1: HCV genotype 2 or 3: participants will receive SOF 400 mg once daily with weight-based RBV for 12 weeks. Participants will be randomized in equal proportions to: no PEG (Arm 1), PEG for 4 weeks (Arm 2), PEG for 8 weeks (Arm 3), or PEG for 12 weeks (Arm 4).
Part 2: HCV genotype 2 or 3: participants will receive SOF 400 mg once daily (monotherapy) for 12 weeks (Arm 5), or SOF 400 mg once daily with PEG and weight-based RBV for 8 weeks (Arm 6); HCV genotype 1: null responders (did not respond to their prior treatment) will receive SOF 400 mg once daily with weight-based RBV for 12 weeks (Arm 7).
Part 3: HCV genotype 1 treatment-naive (Arm 8) or HCV genotype 2 or 3 treatment-experienced participants (Arm 9) will receive SOF 400 mg once daily in combination with weight-based RBV for 12 weeks.
Part 4: HCV genotype 2 or 3 treatment naive participants will receive SOF 400 mg once daily with weight-based RBV for 8 weeks (Arm 10) or SOF 400 mg once daily and 800 mg RBV for 12 weeks (Arm 11). HCV genotype 1 null responders will receive SOF 400 mg once daily, ledipasvir (LDV), and weight based RBV for 12 weeks (Arm 12). HCV genotype-1 treatment naive participants will receive SOF 400 mg once daily with weight-based RBV and LDV for 12 weeks (Arm 13).
Part 5: HCV genotype 1 null responders will receive SOF 400 mg once daily with GS-9669 500 mg once daily and weight-based RBV for 12 weeks (Arm 14). HCV genotype-1 treatment naive participants receive SOF 400 mg once daily with GS-9669 500 mg once daily and weight-based RBV for 12 weeks (Arm 15).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Chronic Genotype 2 or 3 HCV-infection or Genotype 1, serum HCV RNA ≥ 50,000 IU/mL
- •Not co-infected with HIV
- •Use of highly effective contraception methods if female of childbearing potential or sexually active male
Exclusion Criteria
- •History of any other clinically significant chronic liver disease
- •Pregnant or nursing female or male with pregnant female partner
- •History of significant drug allergy to nucleoside/nucleotide analogs.
- •Participation in a clinical study within 3 months prior to first dose
- •Positive result for significant drug use at Screening
Arms & Interventions
Group 1: SOF+RBV 12 wk: GT 2 or 3, TN
Treatment-naive (TN) participants with genotype (GT) 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: SOF (Drug)
Group 1: SOF+RBV 12 wk: GT 2 or 3, TN
Treatment-naive (TN) participants with genotype (GT) 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Intervention: SOF (Drug)
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Intervention: RBV (Drug)
Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.
Intervention: PEG (Drug)
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Intervention: SOF (Drug)
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Intervention: RBV (Drug)
Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.
Intervention: PEG (Drug)
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Intervention: SOF (Drug)
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Intervention: RBV (Drug)
Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.
Intervention: PEG (Drug)
Group 5: SOF 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily for 12 weeks.
Intervention: SOF (Drug)
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Intervention: SOF (Drug)
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Intervention: RBV (Drug)
Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.
Intervention: PEG (Drug)
Group 7: SOF+RBV 12 wk: GT 1, TE
Treatment-experienced (TE) participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: SOF (Drug)
Group 7: SOF+RBV 12 wk: GT 1, TE
Treatment-experienced (TE) participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 8: SOF+RBV 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: SOF (Drug)
Group 8: SOF+RBV 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 9: SOF+RBV 12 wk: GT 2 or 3, TE
Treatment-experienced participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: SOF (Drug)
Group 9: SOF+RBV 12 wk: GT 2 or 3, TE
Treatment-experienced participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 10: SOF+RBV 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 8 weeks.
Intervention: SOF (Drug)
Group 10: SOF+RBV 8 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 8 weeks.
Intervention: RBV (Drug)
Group 11: SOF+RBV 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus split-dose RBV (800 mg in a divided daily dose) for 12 weeks.
Intervention: SOF (Drug)
Group 11: SOF+RBV 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus split-dose RBV (800 mg in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: SOF (Drug)
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: RBV (Drug)
Group 12: SOF+RBV+LDV 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: LDV (Drug)
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: SOF (Drug)
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: RBV (Drug)
Group 13: SOF+RBV+LDV 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.
Intervention: LDV (Drug)
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: SOF (Drug)
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: RBV (Drug)
Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE
Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: GS-9669 (Drug)
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: SOF (Drug)
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: RBV (Drug)
Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.
Intervention: GS-9669 (Drug)
Group 16: LDV/SOF FDC 12 wk: GT 1, fibrosis
Treatment-experienced participants with genotype 1 HCV infection and Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Intervention: LDV/SOF (Drug)
Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis
Treatment-experienced participants with genotype 1 HCV infection with Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis
Treatment-experienced participants with genotype 1 HCV infection with Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: LDV/SOF (Drug)
Group 18: LDV/SOF FDC 12 wk: GT 2 or 3, TN
Treatment-naive participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Intervention: LDV/SOF (Drug)
Group 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE
Treatment-experienced participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.
Intervention: LDV/SOF (Drug)
Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac
Hemophiliac participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: RBV (Drug)
Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac
Hemophiliac participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.
Intervention: LDV/SOF (Drug)
Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 6 weeks.
Intervention: RBV (Drug)
Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 6 weeks.
Intervention: LDV/SOF (Drug)
Group 22: LDV/SOF FDC 6 wk: GT 1, TN
Treatment-naive participants with genotype 1 HCV infection were randomized to receive LDV 90 mg/SOF 400 mg FDC once daily for 6 weeks.
Intervention: LDV/SOF (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Who Experienced Adverse Events
Time Frame: Up to 12 weeks plus 30 days
Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.
Secondary Outcomes
- Percentage of Participants With HCV RNA < LOD at Week 6(Week 6)
- Change From Baseline in HCV RNA at Week 12(Baseline to Week 12)
- Change From Baseline in HCV RNA at Week 8(Baseline to Week 8)
- Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)(Posttreatment Week 12)
- Percentage of Participants With HCV RNA < LOD at Week 8(Week 8)
- Percentage of Participants With Virologic Failure(Up to Posttreatment Week 24)
- Percentage of Participants With HCV RNA < LOD at Week 12(Week 12)
- Change From Baseline in HCV RNA at Week 6(Baseline to Week 6)