A Randomized, Open-Label, Active-Controlled, Multicenter Study to Compare Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Co-Administered With Daclatasvir in Adults With Chronic Hepatitis C Virus Genotype 3 Infection (ENDURANCE-3)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 506
- 主要终点
- Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
研究概览
简要总结
The purpose of this study was to compare the safety and efficacy of ABT-493/ABT-530 to the combination of sofosbuvir (SOF) and daclatasvir (DCV) in adults with genotype 3 (GT3) chronic hepatitis C virus (HCV) infection.
详细描述
This study was a Phase 3, randomized, open-label, active-controlled multicenter study to compare efficacy and safety of ABT-493/ABT-530 to SOF and DCV in treatment-naïve chronic HCV GT3-infected participants without cirrhosis. The study consisted of 2 periods, a treatment period (participants received 8 or 12 weeks of ABT-493/ABT-530 or 12 weeks of SOF with DCV) and a post-treatment period (participants who completed or prematurely discontinued the treatment period were followed for 24 weeks after their last dose of study drug to evaluate efficacy and to monitor HCV RNA and the emergence and persistence of viral variants).
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
- •Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening.
- •Screening laboratory result indicating HCV GT3 infection.
- •Chronic HCV infection, defined as one of the following:
- •Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening; or
- •A liver biopsy consistent with chronic HCV infection; or
- •Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening.
- •Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment).
- •Documented as noncirrhotic.
排除标准
- •Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study.
- •Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could have precluded adherence to the protocol in the opinion of the investigator.
- •Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus Ab (HIV Ab).
- •Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype.
- •Any cause of liver disease other than chronic HCV infection.
- •Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV.
- •History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug.
- •Previous use of any anti-HCV treatment.
研究组 & 干预措施
Arm B
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
干预措施: Sofosbuvir (Drug)
Arm B
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
干预措施: Daclatasvir (Drug)
Arm A
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
干预措施: ABT-493/ABT-530 (Drug)
Arm C
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
干预措施: ABT-493/ABT-530 (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
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. The primary efficacy endpoint was noninferiority in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir \[SOF\] + daclatasvir \[DCV\]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A
时间窗: 12 weeks after the last actual dose of study drug
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.
次要结局
- Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B(12 weeks after the last actual dose of study drug)
- Percentage of Participants With On-treatment Virologic Failure(Treatment weeks 1, 2, 4, 8 (end of treatment for Arm C), and 12 (end of treatment for Arms A and B) or premature discontinuation from treatment)
- Percentage of Participants With Post-treatment Relapse(From the end of treatment through 12 weeks after the last dose of study drug)