Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-9857 in Subjects With Chronic Hepatitis C Virus Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 主要终点
- Percentage of Participants Experiencing Treatment Emergent Adverse Events
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of voxilaprevir (formerly GS-9857) alone or with sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) and antiviral activity of voxilaprevir in adults with genotype 1, 2, 3, 4 hepatitis C virus (HCV) infection. All participants will be monitored for up to 48 weeks after the last dose.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic genotype 1-4 HCV infection
- •For Cohorts 1-9, HCV RNA ≥ 100,000 IU/mL at screening (no HCV RNA restriction for Cohort 10)
- •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
- •Presence of cirrhosis
- •Prior exposure to approved or experimental HCV Protease Inhibitors
- •Co-infection with HIV or hepatitis B virus (HBV)
- •Current or prior history of clinical hepatic decompensation
- •Chronic use of systemic immunosuppressive agents
- •History of clinically significant illness or any other medical disorder that may interfere with participant's treatment, assessment or compliance with the protocol
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Voxilaprevir 300 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Placebo (GT 1a, Cohort 1)
Participants with genotype (GT) 1a HCV infection will receive placebo once daily for 3 days under fasted conditions.
干预措施: Placebo to match voxilaprevir (Drug)
Voxilaprevir 50 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 600 mg (Cohorts 7-9)
Participants with genotypes 1a, 1b, 2, 3, or 4 HCV infection will receive voxilaprevir up to 600 mg under fasted or fed conditions for 3 days.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 300 mg (GT 1a, Cohort 1)
Participants with GT 1a HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Placebo (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive placebo once daily for 3 days under fasted conditions.
干预措施: Placebo to match voxilaprevir (Drug)
Voxilaprevir 50 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg (GT 3, Cohort 2)
Participants with GT 3 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Placebo (GT 2, Cohort 3)
Participants with GT 2 HCV infection will receive placebo once daily for 3 days under fasted conditions.
干预措施: Placebo to match voxilaprevir (Drug)
Voxilaprevir 100 mg (GT 2, Cohort 3)
Participants with GT 2 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg (GT 4, Cohort 4)
Participants with GT 4 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg (GT 1b, Cohort 5)
Participants with GT 1b HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
Participants with GT 3a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fed conditions.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)
Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 after moderate fat meal and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC)on Days 2 and 3 after either a light or moderate-fat meal.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)
Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 after moderate fat meal and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC)on Days 2 and 3 after either a light or moderate-fat meal.
干预措施: SOF/VEL (Drug)
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)
Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal.
干预措施: Voxilaprevir (Drug)
Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)
Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal.
干预措施: SOF/VEL (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment Emergent Adverse Events
时间窗: First dose date up to Day 3 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
时间窗: First dose date up to Day 3 plus 30 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.
Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA
时间窗: Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48
The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6). Data are summarized by treatment/cohort and placebo.
次要结局
- Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA(Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48)
- Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)(Days 4, 5, 6, 7, 8, 10, and Week 48)
- Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48(Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48)