An Open-Label, Sequential Arm, Multicenter Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-267 With and Without Ribavirin (RBV) in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 主要终点
- Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)]
研究概览
简要总结
The purpose of this study was to evaluate the efficacy, safety and pharmacokinetics of ABT-450/r when given together with ABT-267 and with and without RBV in treatment-naïve participants with genotype 1, 2 or 3 chronic HCV infection.
详细描述
This was a 2 sequential arm, combination treatment study where each arm contained 3 cohorts: one each for HCV genotype 1, 2, and 3. The study consisted of 2 phases, a treatment phase and a post-treatment phase. The treatment phase was designed to explore the antiviral activity, safety and pharmacokinetics of ABT-450/r dosed in combination with ABT-267 with and without RBV for up to 12 weeks. The post-treatment phase was designed to monitor and evaluate Sustained Virologic Response (SVR) 12, SVR 24, and the evolution and persistence of viral resistance to ABT-267 and ABT-450 in HCV genotype 1-, 2-, and 3-infected participants who have been exposed to ABT-267 and ABT-450/r. Arms 1 and 2 were enrolled sequentially.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Participants who had a body mass index 18 to < 35 kg/m^
- •Females were either postmenopausal for at least 2 years, surgically sterile, or willing to use at least 2 effective forms of birth control.
- •Males must have been surgically sterile or agreed to use at least 2 effective forms of birth control throughout the course of the study.
- •Participants were in a condition of general good health, other than the HCV infection.
- •Participants had a chronic HCV genotype 1, 2, or 3 infection for at least 6 months, a plasma HCV RNA > 50,000 IU/mL, and FibroTest score <= 0.72 and aspartate aminotransferase (AST) to platelet ratio index <= 2, Fibroscan® result of < 9.6 kilopascal (kPa), or absence of cirrhosis based on a liver biopsy.
排除标准
- •Positive drug screen
- •Previous use of anti-HCV agents
- •History of cardiac disease
- •History of uncontrolled diabetes or diabetes requiring insulin
- •Abnormal laboratory results
- •Females who were pregnant or planned to become pregnant within 6 months after their last dose of study drug/RBV or were breastfeeding; males whose partners were pregnant or would become pregnant within 6 months after their last dose of study drug/RBV
- •Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus (HIV) antibody (Ab). Negative HIV status was to be confirmed at screening.
研究组 & 干预措施
ABT-450/r and ABT-267 plus RBV in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ribavirin (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ritonavir (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ribavirin (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ritonavir (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ribavirin (Drug)
ABT-450/r and ABT-267 plus RBV in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ritonavir (Drug)
ABT-450/r and ABT-267 in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 in genotype 1 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection.
干预措施: ritonavir (Drug)
ABT-450/r and ABT-267 in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 in genotype 2 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection.
干预措施: ritonavir (Drug)
ABT-450/r and ABT-267 in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ABT-450 (Drug)
ABT-450/r and ABT-267 in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ABT-267 (Drug)
ABT-450/r and ABT-267 in genotype 3 participants
ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection.
干预措施: ritonavir (Drug)
结局指标
主要结局
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)]
时间窗: Week 4 through Week 12
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL). Participants with missing data were imputed as failures.
次要结局
- Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment(Post-treatment Day 1 to Post-treatment Week 24)
- Percentage of Participants Who Experienced Virologic Relapse Through End of Post Treatment Period (up to 48 Weeks)(Post-treatment Day 1 to Post-treatment Week 48)
- Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment(Post-treatment Day 1 to Post-treatment Week 12)
- Percentage of Participants With Virologic Failure During Treatment(Day 1 through Week 12)
- Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL)(Week 2)
- Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) at Week 4 Rapid Virologic Response (RVR)(Week 4)