A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared With GS-5885, GS-9451 With Tegobuvir or RBV in Treatment-Experienced Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 170
- 试验地点
- 51
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.
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 ≥18 years with chronic HCV infection
- •Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
- •Monoinfection with HCV genotype (GT) 1a or 1b
- •HCV RNA ≥ 104 IU/mL at screening
- •Prior treatment and adherence with one course of pegylated interferon alfa and RBV
- •The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
- •Body mass index (BMI) 18-40 kg/m2 inclusive
- •Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
- •≤ 450 msec for males and ≤ 470 msec for females.
- •Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
排除标准
- •Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
- •History of significant cardiac disease
- •Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
- •Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
- •Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.
研究组 & 干预措施
Arm 1
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
干预措施: GS-5885 (Drug)
Arm 1
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
干预措施: GS-9451 (Drug)
Arm 1
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
干预措施: tegobuvir (Drug)
Arm 1
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
干预措施: Ribavirin (Drug)
Arm 2
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
干预措施: GS-5885 (Drug)
Arm 2
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
干预措施: GS-9451 (Drug)
Arm 2
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
干预措施: tegobuvir (Drug)
Arm 2
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
干预措施: placebo to match RBV (Drug)
Arm 3
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
干预措施: GS-5885 (Drug)
Arm 3
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
干预措施: GS-9451 (Drug)
Arm 3
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
干预措施: placebo to match tegobuvir (Drug)
Arm 3
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
干预措施: Ribavirin (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 24 weeks
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Antiviral Activity
时间窗: 24 weeks
To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< lower limit of quantitation \[LLoQ\] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection
次要结局
- Antiviral Efficacy(24-48 weeks)
- Viral Dynamics(10 days)
- Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics(predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose)