A Phase 3b, Multi-Center, Randomized, Open-Label, Pragmatic Study of Glecaprevir/Pibrentasvir (G/P) +/- Ribavirin for GT1 Subjects With Chronic Hepatitis C Previously Treated With an NS5A Inhibitor + Sofosbuvir Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 177
- 试验地点
- 31
- 主要终点
- SVR After G/P 12 Wks (Arm A) vs. G/P Given for 16 Weeks (Arm B) to Non-cirrhotic Treatment-experienced GT1 HCV Participants
研究概览
简要总结
The study will enroll well-compensated cirrhotic as well as non-cirrhotic subjects treatment experienced with an NS5a Inhibitor + sofosbuvir and will include patients who did not complete the prescribed duration due to adverse event or any reason other than for non/poor compliance. Subjects will be randomized to 12 or 16 weeks of treatment.
详细描述
The primary purpose of this study is to compare the efficacy and safety of glecaprevir and pibrentasvir (G/P) for 12 weeks to G/P for 16 weeks in non-cirrhotic NS5A (non-structural protein 5a)-inhibitor plus sofosbuvir ± RBV (Ribavirin) treatment-experienced adults with HCV genotype 1 (GT1) infection, and to compare the efficacy and safety of G/P with RBV for 12 weeks to G/P without RBV for 16 weeks in NS5A-inhibitor plus sofosbuvir (SOF) ± RBV treatment-experienced adults with compensated cirrhosis and GT1 infection.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female at least 18 years of age at time of screening.
- •A history of previous treatment with an NS5A-inhibitor plus sofosbuvir therapy ± RBV for chronic HCV genotype 1 infection.
- •Treatment must have been completed at least 1 month prior to Screening Visit.
- •Screening laboratory result indicating chronic HCV GT1 infection. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements and must voluntarily sign and date an informed consent.
排除标准
- •History of severe, life-threatening or other significant sensitivity to any drug.
- •Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is 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 preclude 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 antibody (HIV Ab) in patient without known history of HIV infection.
- •HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
- •History or presence of liver decompensation.
研究组 & 干预措施
Arm A: G/P 300 mg/120 mg QD for 12 Wks
Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks.
干预措施: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (Drug)
Arm B: G/P 300 mg/120 mg QD for 16 Wks
Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks)
干预措施: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (Drug)
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks
Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks)
干预措施: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (Drug)
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks
Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks)
干预措施: Ribavirin 200Mg Tablet (Drug)
Arm D: G/P 300 mg/120 mg QD for 16 Wks
Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks)
干预措施: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (Drug)
结局指标
主要结局
SVR After G/P 12 Wks (Arm A) vs. G/P Given for 16 Weeks (Arm B) to Non-cirrhotic Treatment-experienced GT1 HCV Participants
时间窗: Up to 28 weeks
Number of non-cirrhotic treatment-experienced HCV genotype 1 with a NS5Ai inhibitor + SOF +/-RBV participants with undetectable HCV RNA (HCV RNA \<Lower Limit of Quantification -LLOQ) 12 weeks after completing G/P 300 mg/100 mg daily for 12 weeks (Arm A) vs. 16 weeks of G/P 300 mg/100 mg daily (Arm B)
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks
时间窗: Up to 28 weeks
Number of cirrhotic participants who are treatment experienced with a NS5A inhibitor + SOF +/RBV with undetectable HCV RNA 12 weeks after completing G/P plus RBV for 12 wks vs. G/P for 16 Wks
Tolerability of G/P +/-RBV
时间窗: Up to 16 weeks
Number of subjects who discontinued G/P due to adverse events
次要结局
- Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects(Up to 28 weeks)
- Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects(Up to 28 weeks)
- Difference in % of Relapse Between Cirrhotic Arms C & D(Up to 28 weeks)
- Difference in SVR12 Rates for 12-wk vs 16 wk(28 weeks)
- Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)(Up to 28 weeks)