Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-5816 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
- 103
- 试验地点
- 9
- 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, tolerability, and antiviral activity of velpatasvir (formerly GS-5816) in HCV treatment naive participants with genotypes 1-6.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HCV treatment-naive adult participants (18-65 years of age) with chronic HCV infection and plasma HCV RNA ≥ 5 log10 IU/mL at screening
- •Agree to use protocol defined precautions against pregnancy
排除标准
- •Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
- •Evidence of cirrhosis
- •Evidence of current drug abuse
- •Screening laboratory results outside the protocol specified requirements
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Velpatasvir 5 mg (GT 1a)
Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 5 mg (GT 1a)
Participants with genotype (GT) 1a HCV infection will receive velpatasvir 5 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 25 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 25 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 50 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 50 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 100 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 100 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 100 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 100 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 150 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 150 mg (GT 1a)
Participants with GT 1a HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 150 mg (GT 1b)
Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 150 mg (GT 1b)
Participants with GT 1b HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 150 mg (GT 2)
Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 150 mg (GT 2)
Participants with GT 2 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 25 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 25 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 25 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 50 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 50 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 50 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 150 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 150 mg (GT 3)
Participants with GT 3 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir 150 mg (GT 4)
Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir 150 mg (GT 4)
Participants with GT 4 HCV infection will receive velpatasvir 150 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (Drug)
Velpatasvir up to 400 mg (GT 2)
Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Velpatasvir (Drug)
Velpatasvir up to 400 mg (GT 2)
Participants with GT 2 HCV infection will receive velpatasvir up to 400 mg or placebo once daily for 3 days under fasted conditions.
干预措施: Placebo (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 17 + 2 (Day 19 if Day 17 visit missing)
Treatment-emergent adverse events were defined as any new or worsening adverse event that began on or after the date of the first dose of study drug until the Day 17 study visit date + 2 (Day 19 if Day 17 visit missing).
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
时间窗: First dose date up to Day 17 + 2 (Day 19 if Day 17 visit missing)
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline at any postbaseline visit up to the Day 17 visit date + 2 days (or Day 19 if Day 17 visit was missing). The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), or Grade 3 (severe). Graded laboratory abnormalities were defined using the grading scheme defined in protocol (Gilead Sciences, Inc. Grading Scale for Severity of Adverse Events and Laboratory Abnormalities) for analysis purpose.
Antiviral Activity of Velpatasvir as Measured by Change in Plasma HCV RNA From Baseline
时间窗: Baseline; Days 4, 5, 6, 7, 8, 10, and 17
Participants who were genotyped incorrectly but received appropriate treatment for that genotype were included in that treatment group for the efficacy analysis. Data were summarized by treatment and placebo.
次要结局
- Absolute HCV RNA Level(Baseline; Days 4, 5, 6, 7, 8, 10, and 17)
- PK Parameter of Velpatasvir: AUCtau(0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3)
- Pharmacokinetic (PK) Parameter of Velpatasvir: AUCinf(0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1)
- PK Parameter of Velpatasvir: Ctau(0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 3)
- Number of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected(Days 4, 5, 6, 7, and 8)
- PK Parameter of Velpatasvir: Cmax(0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose.)
- PK Parameter of Velpatasvir: CL/F(0 (predose), 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose at Day 1 for single dose and Day 3 for multiple dose)
- Number of Participants Achieving Reductions From Baseline in HCV RNA(Baseline; Days 4, 5, 6, 7, 8, 10, and 17)
- Plasma HCV RNA Levels by Treatment and IL28B Genotype(Days 4, 5, 6, 7, 8, 10, and 17)
- Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Associated Variants (RAVs) at Pretreatment or Postbaseline Timepoints(First dose date up to Day 17)