A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Four-Drug Regimen and 24 Weeks of a Three-Drug Regimen of GS-9451, Peginterferon Alfa 2a (PEG, Pegasys®) and Ribavirin (RBV, Copegus®) With and Without Tegobuvir (GS-9190) Followed by Response Guided PEG and RBV in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS US 196 0140
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 245
- 试验地点
- 142
- 主要终点
- Sustained virologic response
研究概览
简要总结
This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of a 4-drug regimen with GS-9451 and Tegobuvir and 24 weeks of a 3-drug regimen of GS-9451 without Tegobuvir, all with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®).
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 alanine aminotransferase (ALT), aspartate aminotransferase (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-9451 and Tegobuvir (GS-9190) 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: Tegobuvir (GS-9190) (Drug)
Arm 1
GS-9451 and Tegobuvir (GS-9190) 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-9451 (Drug)
Arm 1
GS-9451 and Tegobuvir (GS-9190) 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-9451 and Tegobuvir (GS-9190) 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-9451 (active) and Tegobuvir (GS-9190) placebo 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-9451 (Drug)
Arm 2
GS-9451 (active) and Tegobuvir (GS-9190) placebo 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: Tegobuvir placebo (Drug)
Arm 2
GS-9451 (active) and Tegobuvir (GS-9190) placebo 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-9451 (active) and Tegobuvir (GS-9190) placebo 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 Tegobuvir (GS-9190) and GS-9451 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: Tegobuvir placebo (Drug)
Arm 3
Placebo matching Tegobuvir (GS-9190) and GS-9451 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-9451 placebo (Drug)
Arm 3
Placebo matching Tegobuvir (GS-9190) and GS-9451 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 Tegobuvir (GS-9190) and GS-9451 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
时间窗: 24 weeks of off-treatment follow-up
Sustained virologic response (SVR) defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after treatment cessation
次要结局
- Safety and tolerability of therapy(Through treatment period and 24 weeks of off-treatment follow-up)
- Emergence of viral resistance following initiation of therapy with GS 9190 and GS 9451(Through 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(Through Week 4 of therapy)
- Durability of response in subjects who achieve SVR(36 months following Week 72)