A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination + Ribavirin Administered in Subjects Infected With Chronic HCV Who Have Advanced Liver Disease or Are Post-Liver Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 339
- 主要终点
- Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
研究概览
简要总结
This study will evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) in participants with advanced liver disease or posttransplant and chronic genotype 1 or 4 hepatitis C virus (HCV) infection.
- Cohort A: decompensated cirrhosis (advanced liver disease), no prior liver transplant;
- Cohort B: post-liver transplant, with or without cirrhosis;
- Group assignment within cohorts is based on severity of liver impairment at screening (Child-Pugh-Turcotte (CPT) score for participants with cirrhosis; fibrosis; or presence of disease for fibrosing cholestatic hepatitis (FCH) groups)
- Randomization is 1:1 within groups to 12 or 24 weeks of LDV/SOF+RBV treatment.
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
- •Able to provide written informed consent
- •Chronic genotype 1 or 4 HCV infection
- •Normal ECG
- •Negative serum pregnancy test for female subjects
- •Male subjects and female subjects of childbearing potential must agree to use contraception
- •Able to comply with the dosing instructions for study drug and able to complete the study schedule of assessments, including all required post treatment visits
排除标准
- •Serious or active medical or psychiatric illness
- •HIV or hepatitis B viral (HBV) infection
- •Stomach disorder that could interfere with the absorption of the study drug
- •Treated with an anti-HCV medication in the last 30 days
- •Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor
- •Use of human granulocyte-macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of screening
- •History of clinically significant medical condition associated with other chronic liver disease
- •Active spontaneous bacterial peritonitis at screening
- •Females who are breastfeeding
- •Infection requiring systemic antibiotics
- •Participated in a clinical study with an investigational drug or biologic within the last 30 days
- •Active or history (last 6 months) of drug or alcohol abuse
- •History of organ transplant other than liver or kidney
研究组 & 干预措施
Cohort A, Group 1 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: LDV/SOF (Drug)
Cohort A, Group 1 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: RBV (Drug)
Cohort A, Group 1 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: LDV/SOF (Drug)
Cohort A, Group 1 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: RBV (Drug)
Cohort A, Group 2 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: LDV/SOF (Drug)
Cohort A, Group 2 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: RBV (Drug)
Cohort A, Group 2 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: LDV/SOF (Drug)
Cohort A, Group 2 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: RBV (Drug)
Cohort B, Group 3 (12 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3.
干预措施: LDV/SOF (Drug)
Cohort B, Group 3 (12 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3.
干预措施: RBV (Drug)
Cohort B, Group 3 (24 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3
干预措施: LDV/SOF (Drug)
Cohort B, Group 3 (24 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3
干预措施: RBV (Drug)
Cohort B, Group 4 (12 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6)
干预措施: LDV/SOF (Drug)
Cohort B, Group 4 (12 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6)
干预措施: RBV (Drug)
Cohort B, Group 4 (24 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6)
干预措施: LDV/SOF (Drug)
Cohort B, Group 4 (24 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6)
干预措施: RBV (Drug)
Cohort B, Group 5 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: LDV/SOF (Drug)
Cohort B, Group 5 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: RBV (Drug)
Cohort B, Group 5 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: LDV/SOF (Drug)
Cohort B, Group 5 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
干预措施: RBV (Drug)
Cohort B, Group 6 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: LDV/SOF (Drug)
Cohort B, Group 6 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: RBV (Drug)
Cohort B, Group 6 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: LDV/SOF (Drug)
Cohort B, Group 6 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
干预措施: RBV (Drug)
Cohort B, Group 7 (12 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with FCH
干预措施: LDV/SOF (Drug)
Cohort B, Group 7 (12 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with FCH
干预措施: RBV (Drug)
Cohort B, Group 7 (24 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with FCH
干预措施: LDV/SOF (Drug)
Cohort B, Group 7 (24 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with FCH
干预措施: RBV (Drug)
结局指标
主要结局
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
时间窗: Up to 24 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
时间窗: Posttreatment Week 12
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
次要结局
- HCV RNA and Change From Baseline at Week 4(Baseline; Week 4)
- Percentage of Participants With HCV RNA < LLOQ at Week 1(Week 1)
- HCV RNA and Change From Baseline at Week 1(Baseline; Week 1)
- HCV RNA and Change From Baseline at Week 2(Baseline; Week 2)
- Percentage of Participants With Virologic Failure(Up to Posttreatment Week 24)
- Percentage of Participants With HCV RNA < LLOQ at Week 2(Week 2)
- Percentage of Participants With HCV RNA < LLOQ at Week 24(Week 24)
- Percentage of Participants With HCV RNA < LLOQ at Week 8(Week 8)
- Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)(Posttreatment Week 8)
- Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12(Posttransplant Week 12)
- Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)(Posttreatment Week 2)
- Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- Percentage of Participants With HCV RNA < LLOQ at Week 4(Week 4)
- Percentage of Participants With HCV RNA < LLOQ at Week 6(Week 6)
- Percentage of Participants With HCV RNA < LLOQ at Week 16(Week 16)
- HCV RNA and Change From Baseline at Week 8(Baseline; Week 8)
- HCV RNA and Change From Baseline at Week 12(Baseline; Week 12)
- Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)(Posttreatment Week 24)
- Percentage of Participants With HCV RNA < LLOQ at Week 20(Week 20)
- Percentage of Participants With HCV RNA < LLOQ at Week 12(Week 12)
- HCV RNA and Change From Baseline at Week 6(Baseline; Week 6)
- Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score(Baseline to Posttreatment Week 4)
- Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score(Baseline to Posttreatment Week 4)