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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 292
- 试验地点
- 2
- 主要终点
- Percentage of Participants Who Experienced Adverse Events
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: LDV/SOF (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced Adverse Events
时间窗: 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.
次要结局
- 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)