A Phase 2 Study to Evaluate the Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 主要终点
- Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
研究概览
简要总结
This study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adult Japanese patients with chronic hepatitis C virus genotype 1b (HCV GT1b) or genotype 2 (HCV GT2) infection who were previous treated with pegylated interferon/ribavirin (pegIFN/RBV).
详细描述
This multicenter, randomized, open-label, parallel-arm, combination treatment study consisted of a Treatment and Post-treatment Phase, divided into 2 cohorts: 1) chronic HCV GT1b- infected, pegIFN/RBV treatment-exposed Japanese adults; and 2) HCV GT2-infected, pegIFN/RBV treatment-exposed Japanese adults. The Treatment Phase evaluated the antiviral activity, safety, and pharmacokinetics of a range of ABT-450/r and ABT-267 doses for 12 to 24 weeks. The Post-treatment Phase evaluated the evolution and persistence of viral resistance to ABT-267 and ABT-450.
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 75 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 post-menopausal for more than 2 years or surgically sterile
- •Chronic hepatitis C, genotype 1b (HCV-GT1b) or genotype 2 (HCV GT2) infection (HCV RNA level greater than 10,000 IU/mL at screening) previously treated with pegylated interferon/ribavirin (pegIFN/RBV).
- •Subject's hepatitis C virus genotype is subgenotype 1b and subject was a null responder or partial responder, OR
- •Subject's hepatitis C virus genotype is subgenotype 2 and subject was a null responder, partial responder, or relapser (Null responder: received at least 10 weeks of pegIFN/RBV for the treatment of HCV and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12; Partial responders: received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved ≥ 2 log10 IU/mL reduction in HCV RNA at Week 12, but failed to achieve HCV RNA undetectable (HCV RNA < lower limit of detection [< LLOD]) at the end of treatment; Relapsers: received at least 1 course of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 24 weeks of treatment follow-up).
排除标准
- •Significant liver disease with any cause other than HCV as the primary cause
- •Positive screen for drugs or alcohol.
- •Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody.
- •Use of contraindicated medications within 2 weeks of dosing
- •Previous use of any investigational or commercially available anti-Hepatitis C virus agent other than pegIFN/RBV, including previous exposure to ABT-450 or ABT-267.
研究组 & 干预措施
Arm 1
Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
Arm 2
Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
Arm 3
Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 24 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
Arm 4
Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 24 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
Arm 5
Participants with HCV GT2 received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
Arm 6
Participants with HCV GT2 received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
干预措施: ABT-450/ritonavir, ABT-267 (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
时间窗: 24 weeks after last dose of study drug
The percentage of participants with SVR24 (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\] 24 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
Number of Participants With Adverse Events (AEs)
时间窗: TEAEs: up to 16 weeks for the 12-week treatment groups and up to 28 weeks for the 24-week treatment groups; SAEs: up to 65 weeks for the 12-week treatment groups and up to 77 weeks for the 24-week treatment groups.
An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose.
次要结局
- Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12)(12 weeks after last dose of study drug)
- Percentage of Participants With End of Treatment (EOT) Response(12 or 24 weeks after first dose of study drug)