A Phase 2, Randomized, Open-label Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 6 or 8 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Subjects With Chronic Hepatitis C Virus Genotype 1 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 主要终点
- Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early stages of liver fibrosis or with cirrhosis.
详细描述
This is an open-label (participants and researchers are aware about the treatment participants are receiving), and multicenter (when more than 1 hospital or medical school team work on a medical research) study. The study will consist of a Screening Phase (6 weeks); an Open-label Treatment Phase (6 weeks for Arm A and 8 weeks for Arm B); and a Post-treatment Follow-up Phase (until 24 weeks after end of study treatment). Using a staggered approach, all eligible participants will be assigned to 1 of the 2 arms, according to their level of fibrosis. Arm A (consists of chronic HCV genotype 1 infected participants with early stages of liver fibrosis): participants will receive a combination therapy of SMV 150 milligram (mg), DCV 60 mg and SOF 400 mg once daily for 6 weeks. Arm B (consists of chronic HCV genotype 1 infected participants with cirrhosis): participants will receive a combination therapy of SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. A sub-study will be performed at a selected study site, where only participants who will be eligible to participate in both the main study and the sub-study will be enrolled. Intra-hepatic and plasma HCV ribonucleic acid (RNA) levels; intra-hepatic, peripheral innate and adaptive immune responses during the treatment, will be assessed in the sub-study. Participants' safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000 international units per milliliter (IU/mL), both determined at Screening
- •Participants of Arm A should have evidence of early stages of liver fibrosis, defined by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to platelet ratio index (APRI) score <=1
- •Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a METAVIR score F
- •In addition, participants should have absence of esophageal varices or presence of small (grade 1) esophageal varices determined by upper gastrointestinal endoscopy, and absence of findings indicative of hepatocellular carcinoma in an ultrasonography
- •HCV treatment-naive, defined as not having received treatment with any approved or investigational drug for chronic HCV infection
- •Pegylated interferon (PegIFN) and ribavirin (RBV) eligible, defined as not having any contraindication to the use of PegIFN and RBV, in line with the prescribing information for each compound
排除标准
- •A. Main Study:
- •Co-infection with HCV of another genotype than genotype 1 and/or human immunodeficiency virus (HIV) type 1 or 2 (positive HIV-1 or HIV 2 antibody test at Screening)
- •Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, hepatitis B infection (hepatitis B surface antigen positive), drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator
- •Evidence of clinical hepatic decompensation or presence of grade 2/3 esophageal varices
- •Any of the protocol defined laboratory abnormalities
- •B. Sub-study:
- •Presence of coagulopathy (hemophilia) or hemoglobinopathy (including sickle cell disease, thalassemia)
- •Use of any anti-coagulant (for example, warfarin, heparin) or anti-platelet medications within 1 week of the Screening visit
- •Any of the protocol defined laboratory abnormalities
研究组 & 干预措施
Arm A
Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks.
干预措施: Simeprevir 150 mg (Drug)
Arm A
Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks.
干预措施: Daclatasvir 60 mg (Drug)
Arm A
Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks.
干预措施: Sofosbuvir 400 mg (Drug)
Arm B
Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks.
干预措施: Simeprevir 150 mg (Drug)
Arm B
Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks.
干预措施: Daclatasvir 60 mg (Drug)
Arm B
Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks.
干预措施: Sofosbuvir 400 mg (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)
时间窗: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)
Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment.
次要结局
- Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment(4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B))
- Percentage of Participants With On-treatment Virologic Response(Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only))
- Percentage of Participants With On-Treatment Failure(Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B))
- Number of Participants With Viral Relapse(From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B))
- Number of Participants With Late Viral Relapse(From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B))
- Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR(Up to Week 30 for Arm A and up to Week 32 for Arm B)
- Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR(up to Week 30 for Arm A and Week 32 for Arm B)