A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks With Ribavirin or for 24 Weeks Without Ribavirin in Treatment-Experienced Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 155
- 主要终点
- Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
研究概览
简要总结
This study is to determine the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) with and without ribavirin (RBV), and to evaluate the safety and tolerability of each regimen as assessed by review of the accumulated safety data. Approximately 150 participants with genotype 1 HCV infection, who have previously received treatment for HCV, and who have a diagnosis for cirrhosis will be enrolled. Participants will be randomized to 1 of 2 groups.
Group 1: SOF/LDV FDC tablet plus placebo to match RBV for 24 weeks
Group 2: Delayed treatment group: placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by SOF/LDV FDC once daily plus RBV in a divided daily dose for 12 weeks
Randomization will 1:1 to the two groups and will be stratified by HCV genotype (1a, 1b; mixed or other genotype 1 results will be stratified as genotype 1a), and prior HCV therapy treatment response (never achieved HCV RNA < the lower limit of quantitation (LLOQ), or achieved HCV RNA < LLOQ).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
- •HCV RNA ≥ 10,000 IU/mL at screening
- •Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and a protease inhibitor following documented prior virology failure after treatment with a PEG-IFN + RBV regimen
- •Evidence of cirrhosis
- •Screening laboratory values within defined thresholds
- •Use of two effective contraception methods if female of childbearing potential or sexually active male
排除标准
- •Pregnant or nursing female or male with pregnant female partner
- •Current or prior history of clinical hepatic decompensation
- •Prior exposure to approved or experimental HCV specific direct-acting antivirals other than a nonstructural protein (NS)3/4A protease inhibitor
- •History of solid organ transplantation, including liver transplant
- •Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
- •Chronic use of systemic immunosuppressive agents
- •History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
研究组 & 干预措施
LDV/SOF
LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
干预措施: Placebo to match RBV (Drug)
LDV/SOF
LDV/SOF FDC tablet plus placebo to match RBV for 24 weeks
干预措施: LDV/SOF (Drug)
LDV/SOF + RBV
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
干预措施: LDV/SOF (Drug)
LDV/SOF + RBV
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
干预措施: RBV (Drug)
LDV/SOF + RBV
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
干预措施: Placebo to match LDV/SOF (Drug)
LDV/SOF + RBV
Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks.
干预措施: Placebo to match RBV (Drug)
结局指标
主要结局
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, \< 25 IU/mL) 12 weeks following the last dose of study drug. * 1 participant who was randomized to the LDV/SOF + RBV group who received placebo discontinued prior to receiving LDV/SOF + RBV and is excluded from the Full Analysis Set. * 1 participant who was randomized to the LDV/SOF + RBV group received LDV/SOF + placebo, and is counted in the LDV/SOF group for the safety analysis, and in the LDV/SOF+RBV group for the efficacy analysis (ie, in the Full Analysis Set).
次要结局
- Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)(Posttreatment Weeks 4 and 24)
- Percentage of Participants With HCV RNA < LLOQ (ie, < 25 IU/mL) at Weeks 1, 2, 4, 8, 12, and 24(Weeks 1, 2, 4, 8, 12, and 24)
- Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12(Baseline; Weeks 1, 2, 4, 8, and 12)
- Percentage of Participants With Virologic Failure(Baseline to Posttreatment Week 24)