A Phase 2b, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GS 9450 in Adults With Chronic Hepatitis C Virus Infection (GS-US-227-0106)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 307
- 主要终点
- Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
研究概览
简要总结
This is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, multicenter study investigating the safety, tolerability and efficacy of two oral doses of GS-9450 in adults with chronic Hepatitis C Virus (HCV). Approximately 240 subjects 18-65 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of three treatment groups (80 subjects per treatment group) as follows:GS-9450 10 mg once daily,GS-9450 40 mg once daily, or matching placebo once daily.
Following randomization, subjects will return within seven business days for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 26 week treatment phase. During the treatment phase, subjects will receive study drug once daily for 24 weeks and then taper off of study drug over the following 2 weeks by receiving study drug once every other day for one week and then every 3 days for one week. Following completion of the treatment phase, subjects will enter a 4-week off-treatment follow-up phase.
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
- 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
- •Adult subjects, ages 18-65
- •Chronic HCV infection, defined as having documented HCV infection (antibody or RNA positivity) at least 6 months prior to Baseline (Day 1) with HCV viremia at screening
- •Screening Knodell necroinflammatory score >= 3 based on liver biopsy evaluation (as determined by local pathologist) conducted anytime during the 45-day screening period
- •ALT > the upper limit of the normal range (ULN) but < 10 X ULN at the screening visit
- •Previously failed pegylated interferon-based HCV therapy in combination with ribavirin therapy, or is unable to tolerate or has contraindications to receiving interferon or ribavirin therapy
- •BMI between 19 and 36 kg/m2 (inclusive)
- •Creatinine clearance >= 70 mL/min
- •absolute neutrophil count >= 1000/mm3
- •Hemoglobin > 10 g/dL
- •Have no clinical or laboratory evidence of hepatic decompensation
排除标准
- •Decompensated liver disease
- •Child-Pugh grade B or C cirrhosis
- •Evidence of hepatocellular carcinoma
- •Positive urine drug screen for cocaine or amphetamines
- •Infection with HCV genotype 3
- •Co-infection with hepatitis B virus or human immunodeficiency virus
- •Pancreatitis
- •Recent significant infection or symptoms of infection
- •Autoimmune disorders
- •Any history of seizure
- •Is a public transportation operator (pilot of airplane or ship; air traffic controller; bus, train or subway driver) or operates heavy construction machinery
- •Transplantation
- •History of malignancy
- •Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males
- •History of or current binge drinking
研究组 & 干预措施
GS-9450 10 mg/day
GS-9450 taken as one 10 mg capsule by mouth once daily
干预措施: GS-9450 (Drug)
GS-9450 40 mg/day
GS-9450 taken as one 40 mg capsule by mouth once daily
干预措施: GS-9450 (Drug)
Placebo
Placebo taken as one placebo capsule by mouth once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
时间窗: Week 24 on-treatment
次要结局
- Change (absolute, percent) from baseline in the Knodell necroinflammatory score(Baseline to Week 24)
- Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels(Baseline to Week 24)
- Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities(Up to 24 weeks plus 30 days following the last dose of study drug)
- Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels(Baseline to Week 24)
- Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens(Baseline to Week 24)
- Change from baseline in the percent of apoptotic cells(Baseline to Week 24)
- Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes(Baseline to Week 24)
- Change From Baseline in HCV RNA(Baseline to to Week 24)