A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 184
- 主要终点
- Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
研究概览
简要总结
The purpose of this study in HCV genotype 4-infected participants with compensated cirrhosis is to assess the safety and to compare the percentage of participants achieving a 12-week sustained virologic response (SVR12), [HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks following treatment], to a clinically relevant threshold [based on SVR rates for HCV genotype 4-infected participants treated with pegylated interferon (pegIFN)/RBV].
详细描述
This is a Phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of ombitasvir/paritaprevir/ritonavir coadministered with RBV for 12, 16, or 24 weeks in HCV genotype 4 (GT4)-infected participants with compensated cirrhosis who are either treatment-naïve or who had previously received only IFN/RBV treatment for HCV.
The study also enrolled HCV GT4-infected participants with compensated cirrhosis who had previously experienced virologic failure with either SOF/pegIFN/RBV or sofosbuvir (SOF)/RBV treatment. These participants were treated with ombitasvir/paritaprevir/ritonavir coadministered with RBV for 24 weeks in this study.
This study was divided into 2 parts with approximately 184 total participants. Part I included participants who were randomized to receive either 12 or 16 weeks of treatment and Part II included participants who received 24 weeks of treatment. Enrollment into Part II opened once randomization in Part I was completed.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For Arms A, B and C:
- •Participants must meet one of the following:
- •Treatment-naive: Participant has never received antiviral treatment for hepatitis C infection OR
- •Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV);
- •Participant must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories:
- •Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV;
- •Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy.
- •For Arms A, B, C and D:
- •Chronic HCV genotype 4 infection with cirrhosis.
- •Participant has plasma HCV RNA level > 1,000 IU/mL at Screening
排除标准
- •Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
- •Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or Nonstructural viral protein (NS) 5A inhibitor, either investigational or commercially available (including previous exposure to paritaprevir or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or SOF with RBV is required.
- •Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy.
- •Confirmed presence of hepatocellular carcinoma.
- •Any cause of liver disease other than chronic HCV infection.
- •Abnormal laboratory tests.
研究组 & 干预措施
Arm A
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 12 weeks for genotype 4 treatment-naïve or treatment-experienced with IFN/RBV.
干预措施: ombitasvir/paritaprevir/ritonavir (Drug)
Arm A
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 12 weeks for genotype 4 treatment-naïve or treatment-experienced with IFN/RBV.
干预措施: ribavirin (Drug)
Arm B
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 16 weeks for genotype 4 treatment-naive or treatment-experienced with IFN/RBV.
干预措施: ombitasvir/paritaprevir/ritonavir (Drug)
Arm B
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 16 weeks for genotype 4 treatment-naive or treatment-experienced with IFN/RBV.
干预措施: ribavirin (Drug)
Arm C
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 treatment-naive and treatment-experienced with IFN/RBV.
干预措施: ombitasvir/paritaprevir/ritonavir (Drug)
Arm C
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 treatment-naive and treatment-experienced with IFN/RBV.
干预措施: ribavirin (Drug)
Arm D
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 SOF/pegIFN/RBV or SOF/RBV treatment-experienced.
干预措施: ombitasvir/paritaprevir/ritonavir (Drug)
Arm D
Ombitasvir/paritaprevir/ritonavir (25/150/100 mg) and Ribavirin dosed for 24 weeks for genotype 4 SOF/pegIFN/RBV or SOF/RBV treatment-experienced.
干预措施: ribavirin (Drug)
结局指标
主要结局
Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
时间窗: 12 weeks after the last actual dose of study drug
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (\<LLOQ) 12 weeks after the last dose of study drug.
次要结局
- Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B)(12 weeks after the last actual dose of study drug)
- Percentage of Participants With SVR12 in Participants Receiving 16 Weeks (Arm B) of Treatment Compared to Participants Receiving 24 Weeks of Treatment (Arm C)(12 weeks after the last actual dose of study drug)
- Percentage of Participants in Arms A, B and C With On-treatment Virologic Failure(Up to Treatment Week 24 (end of treatment) or premature discontinuation from treatment)
- Percentage of Participants in Arms A, B and C With Post-treatment Relapse(From the end of treatment through 12 weeks after the last dose of study drug)