A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Response Guided Therapy With GS-9190, GS-9256, Ribavirin (Copegus®) and Peginterferon Alfa 2a (Pegasys®) in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0123)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 324
- 试验地点
- 114
- 主要终点
- Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation
研究概览
简要总结
This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of response-guided duration of therapy with GS-9190 and GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®). Additionally, the efficacy and safety of 24 weeks of GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) will be evaluated.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects 18 to 70 years of age
- •Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
- •Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
- •Monoinfection with HCV genotype 1a or 1b
- •HCV treatment-naïve
- •Body mass index (BMI) between 18 and 36 kg/m2
- •Creatinine clearance >/= 50 mL/min
- •Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
- •Screening laboratory values within defined thresholds for ALT, AST, leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH), potassium, magnesium
排除标准
- •Autoimmune disease
- •Decompensated liver disease or cirrhosis
- •Poorly controlled diabetes mellitus
- •Severe psychiatric illness
- •Severe chronic obstructive pulmonary disease (COPD)
- •Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
- •Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
- •History of hemoglobinopathy
- •Known retinal disease
- •Subjects who are immunosuppressed
- •Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
- •Subjects who are on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of Baseline (Day 1) or during the study
- •Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening
研究组 & 干预措施
Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: GS-9190 (Drug)
Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: GS-9256 (Drug)
Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: Pegasys® (Biological)
Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: Copegus® (Drug)
Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: GS-9190 placebo (Drug)
Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: GS-9256 (Drug)
Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: Pegasys® (Biological)
Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
干预措施: Copegus® (Drug)
Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
干预措施: GS-9190 placebo (Drug)
Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
干预措施: GS-9256 placebo (Drug)
Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
干预措施: Pegasys® (Biological)
Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
干预措施: Copegus® (Drug)
结局指标
主要结局
Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation
时间窗: 24 weeks of off-treatment follow-up
次要结局
- Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events(Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up)
- Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256(Through up to 48 weeks treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy)
- Viral dynamics and steady state pharmacokinetics of GS-9190 and GS-9256 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9256 over time(Through Week 4 of therapy)
- Long-term assessment of plasma HCV RNA in subjects who achieve SVR(36 months following Week 72)