A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 316
- 主要终点
- Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.
详细描述
This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.
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
- None
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
- •Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile
- •Subjects must meet one of the following:
- •Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR
- •Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV);
- •Body mass index (BMI) is ≥ 18 to < 38 kg/m^
- •Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening.
- •Subject has plasma HCV RNA level > 10,000 IU/mL at Screening
排除标准
- •History of severe, life-threatening or other significant sensitivity to any drug.
- •Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV.
- •Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
- •Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.
研究组 & 干预措施
Group 1
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
干预措施: ABT-450/r (Drug)
Group 1
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
干预措施: ABT-267 (Drug)
Group 2
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants
干预措施: ABT-450/r (Drug)
Group 2
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants
干预措施: ABT-267 (Drug)
Group 3
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants
干预措施: ABT-450/r (Drug)
Group 3
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants
干预措施: ABT-267 (Drug)
Group 4
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
干预措施: ABT-450/r (Drug)
Group 4
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
干预措施: ABT-267 (Drug)
Group 4
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
干预措施: Ribavirin (RBV) (Drug)
Group 5
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants
干预措施: ABT-450/r (Drug)
Group 5
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants
干预措施: ABT-267 (Drug)
Group 6
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
干预措施: ABT-450/r (Drug)
Group 6
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
干预措施: ABT-267 (Drug)
Group 6
ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
干预措施: Ribavirin (RBV) (Drug)
Group 7
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis
干预措施: ABT-450/r (Drug)
Group 7
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis
干预措施: ABT-267 (Drug)
Group 8
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis
干预措施: ABT-450/r (Drug)
Group 8
ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis
干预措施: ABT-267 (Drug)
结局指标
主要结局
Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
时间窗: 12 weeks after the last actual dose of study drug
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\<LLOQ\]) 12 weeks after the last dose of study drug.
次要结局
- Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment(24 weeks after the last actual dose of study drug)
- Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.(Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8)
- Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.(Within 12 weeks after the last dose of study drug)
- Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events(From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8.)