A Randomized Controlled Study To Assess Safety, Tolerability And Efficacy Of GS-7977 In Combination With Full or Low Dose RBV In HCV Genotype 1, Monoinfected Treatment Naive Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Participants With Adverse Events
研究概览
简要总结
Background:
- GS-7977 is a new drug that is being developed to treat hepatitis C infection. It works by blocking the hepatitis C virus from dividing in the body. This medication has been used along with other medications commonly used to treat hepatitis C, such as interferon and ribavirin. When used with interferon and ribavirin, GS-7977 seems to be very effective in eliminating the hepatitis C virus from the body. However, interferon can have serious side effects, so researchers want to see if GS-7977 can work by itself or with only ribavirin.
Objectives:
- To test the safety and effectiveness of GS-7977 alone or given with ribavirin for hepatitis C infection.
Eligibility:
- Individuals at least 18 years of age who have hepatitis C with liver disease, and have never received drugs for it.
Design:
- This study will require multiple clinic visits over 18 months. A liver biopsy will be required before the start of the study if participants have not had one within the past 3 years.
- Participants will be screened with a medical history and physical exam.
- Participants will have either GS-7977 alone or GS-7977 with ribavirin. GS-7977 is taken by mouth once a day. Ribavirin is taken by mouth in the morning and evening.
- Participants will have study visits on Days 1, 3, 5, 7, 10, and 14. These visits will involve regular blood tests and symptom monitoring.
- After the second week, participants will have study visits during Weeks 3, 4, 6, 8, 12, 16, and 20. Blood and urine tests will be given to study virus levels in the body, and symptoms will be discussed.
- Participants will stop receiving the study drugs at Week 24.
- Followup clinic visits with blood tests will take place in Weeks 28, 36, 48, 52, 60, and 72. Another liver biopsy will be performed at 48 weeks.
- Some participants may also be part of a smaller study. This study involves frequent blood draws to study drug and virus levels in the blood. The study will require a 36-hour hospital inpatient visit.
详细描述
Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. A combination of ribavirin (RBV) and pegylated interferon (PegIFN) is the currently recommended therapy for chronic HCV infection and this may achieve viral clearance in 19% to 52% of patients infected with HCV genotype 1 (GT-1) and in 76% -80% of patients infected with HCV genotypes 2 and 3. The standard of care is changing and will soon become an HCV protease inhibitor [Boceprevir/ Telaprevir in combination with PegIFN and RBV]. The registration studies for the new protease inhibitors demonstrated increased sustained virologic response (SVR) rates of 60 70%. However, this is still associated with a high incidence of adverse events (AEs) and lower cure rates in several populations. Novel therapies that do not rely on an Interferon backbone will be required to enhance cure rates in various populations.
This is a randomized controlled open-label study to assess safety, tolerability and efficacy of GS-7977 (a potent and selective HCV NS5B inhibitor) given at a dose of 400 mg daily in combination with RBV to a total of 60 treatment-na(SqrRoot) ve HCV genotype 1 mono-infected individuals with less than or equal to stage 2 fibrosis.
The findings from this study will aid in the understanding of antiviral and host responses to an interferon (IFN) free regimen as well as determine the role of RBV in IFN-free therapies.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 2 Arm B
(N = 25): 24 weeks of GS-7977 QD with low dose RBV (600mg).
干预措施: RBV (Drug)
Phase 1
Participants (N =10) will receive GS-7977 QD in combination with RBV for a total of 24 weeks. The study team will perform an interim evaluation of data and safety at the end of 12 weeks of treatment.
干预措施: GS7977 (Drug)
Phase 1
Participants (N =10) will receive GS-7977 QD in combination with RBV for a total of 24 weeks. The study team will perform an interim evaluation of data and safety at the end of 12 weeks of treatment.
干预措施: RBV (Drug)
Phase 2 Arm A
(N =25) 24 weeks of GS-7977 QD in combination with weight based RBV (1000 mg for participants weighing <75 kg and 1200 mg for participants weighing ≥75kg)
干预措施: GS7977 (Drug)
Phase 2 Arm A
(N =25) 24 weeks of GS-7977 QD in combination with weight based RBV (1000 mg for participants weighing <75 kg and 1200 mg for participants weighing ≥75kg)
干预措施: RBV (Drug)
Phase 2 Arm B
(N = 25): 24 weeks of GS-7977 QD with low dose RBV (600mg).
干预措施: GS7977 (Drug)
结局指标
主要结局
Participants With Adverse Events
时间窗: 24 weeks
Number of participants with Grade 3-4 Adverse Events During the Study Treatment Period as a measure of safety and tolerability.
Sustained Virologic Response
时间窗: 24 weeks post treatment completion
Sustained virology response at 24 weeks post treatment completion
次要结局
未报告次要终点