A Phase 2b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 122
- 主要终点
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
研究概览
简要总结
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Hemophilia A, B or C, or Von Willebrand's disease
- •Chronic genotype 1, 2, 3 or 4 HCV infection
- •HCV RNA ≥ 1000 IU/mL at screening
- •Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
- •Screening laboratory values within defined thresholds
- •For HIV-1/HCV co-infected individuals:
- •Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
- •Stable protocol-approved ARV regimen for > 8 weeks prior to screening
- •CD4 T-cell count > 200 cells/mm^3 at screening
排除标准
- •Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
- •Current or prior history of any of the following:
- •Hepatic decompensation
- •Chronic liver disease of a non-HCV etiology
- •Hepatocellular carcinoma (HCC)
- •Infection with hepatitis B virus (HBV)
- •Pregnant or nursing female
- •Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
- •Chronic use of systemically administered immunosuppressive agents
- •For HIV-1/HCV co-infected individuals:
- •Opportunistic infection within 6 months prior to screening
- •Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline
研究组 & 干预措施
LDV/SOF GT 1 or 4
Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
干预措施: LDV/SOF (Drug)
SOF+RBV 12 wks GT 2
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
干预措施: SOF (Drug)
SOF+RBV 12 wks GT 2
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
干预措施: RBV (Drug)
SOF+RBV 24 wks GT 3
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
干预措施: SOF (Drug)
SOF+RBV 24 wks GT 3
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
干预措施: RBV (Drug)
结局指标
主要结局
Percentage of Participants Who Permanently Discontinued Any 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
- Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)(Posttreatment Week 4)
- Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)(Weeks 4, 8, 12, 16, 20, and 24)
- Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24(Weeks 1, 2, 4, 8, 12, 16, 20, and 24)
- Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24(Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24)
- Percentage of Participants With Virologic Failure(Up to Posttreatment Week 24)
- Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)(Baseline; Weeks 12, 24, and Posttreatment Week 12)