A Phase II Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172, MK-8742, and Sofosbuvir in Treatment-Naïve Subjects With Chronic HCV GT1 or GT3 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 主要终点
- Number of Participants Experiencing at Least 1 Adverse Event (AE)
研究概览
简要总结
This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).
详细描述
The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.
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
- •has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening
- •has documented chronic HCV GT1 or GT3 infection
- •has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®)
- •is treatment naïve to all anti-HCV treatment
排除标准
- •has evidence of decompensated liver disease
- •is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
- •has a history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy
- •has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
- •has clinically-relevant drug or alcohol abuse within 12 months of screening
- •has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
- •has a history of chronic hepatitis not caused by HCV
研究组 & 干预措施
GT1:NC Grazoprevir/Elbasvir+SOF 4wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT1:NC Grazoprevir/Elbasvir+SOF 4wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned).
干预措施: Sofosbuvir (Drug)
GT1:NC Grazoprevir/Elbasvir+SOF 6wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT1:NC Grazoprevir/Elbasvir+SOF 6wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned).
干预措施: Sofosbuvir (Drug)
GT1:C Grazoprevir/Elbasvir+SOF 6wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT1:C Grazoprevir/Elbasvir+SOF 6wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned).
干预措施: Sofosbuvir (Drug)
GT1:C Grazoprevir/Elbasvir+SOF 8wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT1:C Grazoprevir/Elbasvir+SOF 8wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned).
干预措施: Sofosbuvir (Drug)
GT3:NC Grazoprevir/Elbasvir+SOF 8wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT3:NC Grazoprevir/Elbasvir+SOF 8wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned).
干预措施: Sofosbuvir (Drug)
GT3:NC Grazoprevir/Elbasvir+SOF 12wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT3:NC Grazoprevir/Elbasvir+SOF 12wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned).
干预措施: Sofosbuvir (Drug)
GT3:C Grazoprevir/Elbasvir+SOF 12wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned).
干预措施: Grazoprevir/Elbasvir FDC (Drug)
GT3:C Grazoprevir/Elbasvir+SOF 12wk
Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned).
干预措施: Sofosbuvir (Drug)
结局指标
主要结局
Number of Participants Experiencing at Least 1 Adverse Event (AE)
时间窗: Up to Week 14
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Discontinuing Study Therapy Due to an AE
时间窗: Up to Week 12
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)
时间窗: Up to 24 weeks
The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
次要结局
- Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)(Up to 16 weeks)