Efficacy and Safety Study of GS-9256 and GS-9190 Alone and in Combination With Ribavirin for 28 Days in Patients With Chronic Hepatitis C Virus Infection
A Phase 2, Randomized, Open-Label Trial of GS-9256 Plus GS-9190 Alone and in Combination With Ribavirin for 28 Days in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0112)
This a phase 2, randomized, open-label trial of GS-9256 plus GS-9190, two oral anti HCV drugs, for 28 days with and without ribavirin (RIBA) and with pegylated interferon (PEG)/RIBA in adults with chronic Hepatitis C virus (HCV). In Part A, approximately thirty (30) subjects 18-70 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of the two treatment groups (GS-9256 plus GS-9190 or GS-9256 plus GS-9190 plus RIBA). In Part B, an additional fifteen (15) subjects will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).
Following randomization, subjects will return for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 28 day treatment phase. During the treatment phase, subjects will receive oral study drugs twice daily for 28 days and PEG once weekly for Part B. Subjects then receive PEG/RIBA as local SOC starting on Day 28 (not provided as part of the study). Following completion of the 28-day treatment phase, subjects will be followed for approximately 72 weeks.
研究概览
详细说明
GS-9256 (an HCV NS3 protease inhibitor) plus GS-9190 (non-nucleoside HCV NS5B inhibitor) will be administered for 28 days with and without RIBA (weight-based dosing) and with PEG/RIBA in treatment-naïve subjects with chronic genotype 1 HCV infection. In Part A, thirty (30) subjects with genotype 1 will be randomized to 75 mg GS-9256 BID plus 40 mg GS-9190 BID or 75 mg GS-9256 BID plus 40 mg GS-9190 BID plus RIBA 1000-1200 mg/day for 28 days. In Part B, an additional fifteen (15) subjects with genotype 1 will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA for 28 days. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).
In Part A, for any subjects meeting pre-defined, individual, virologic criteria, PEG/RIBA standard of care will be started prior to Day 28.
Both PEG and RIBA will be administered at their currently approved dosages for treatment of HCV infection in accordance with appropriate labeling. Subjects will be monitored for safety (including ECG monitoring), antiviral activity, pharmacokinetics, and resistance 2-3 times weekly through Day 28.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Adult subjects, ages 18-70
- Willing able to provide informed consent
- BMI between 18 and 36 kg/m2 (inclusive)
- Chronic HCV infection, genotype 1
- HCV RNA >/= 3 log, but < 7.2 log10 IU/ml at screen
- Liver biopsy, FibroTest, or FibroScan indicating absence of cirrhosis
- HCV treatment naïve with imminent plans to start treatment with PEG/RIBA
- QTcF </= 450 msec at screen
- ALT, AST, GGT < 5 X ULN at the screening visit
- Creatinine clearance >= 50 mL/min
- Absolute neutrophil count >= 1500/mm3
- Hemoglobin >/= 12 g/dL (female), >/= 13 g/dL (male)
- Males agree to use of effective contraception and refrain from sperm donation
- Able to comply with dosing instructions and study visits
- Of generally good health
Exclusion Criteria:
- Females of child-bearing potential or males with female partners who are pregnant or planning to become pregnant
- Infection with other HCV genotype or multiple HCV genotypes
- Poorly controlled diabetes
- Hemoglobinopathy or known retinal disease
- History of sarcoidosis or invasive malignancy
- Untreated or significant psychiatric illness
- Co-infection with hepatitis B virus or human immunodeficiency virus
- Chronic use of systemic immunosuppressive agents
- Autoimmune disorders
- Severe COPD
- History of significant cardiac disease
- Known cirrhosis
- Non-HCV chronic liver disease
- Transplantation
- Suspicion of hepatocellular carcinoma
- Bilirubin above the normal range or Gilbert's syndrome
- Decompensated liver disease
- Clinically significant illness
- GI disease that could interfere with absorption
- Acute porphyria
- Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males or current binge drinking
- Positive urine drug screen
- History of difficult blood collection
- Significant recent blood loss
- Prohibited medications, including H2 antagonists, investigational agents
- Restricted fruits, fruit juices
- Hypersensitivity
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：手臂 1
|
75 mg BID x 28 days
40 mg BID x 28 days
|
|
实验性的：手臂 2
|
75 mg BID x 28 days
40 mg BID x 28 days
1000-1200 mg/day given BID
其他名称：
|
|
实验性的：手臂 3
|
75 mg BID x 28 days
40 mg BID x 28 days
1000-1200 mg/day given BID
其他名称：
180 ug q week
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Percentage of subjects achieving rapid virologic response (RVR)
大体时间：Day 28
|
Day 28
|
|
AEs, physical examination and clinical laboratory test findings, vital signs, ECGs
大体时间：Throughout first six weeks of study
|
Throughout first six weeks of study
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Plasma pharmacokinetics
大体时间：Throughout Day 28
|
Throughout Day 28
|
|
Viral resistance
大体时间：Throughout study
|
Throughout study
|
合作者和调查者
调查人员
- 研究主任：Juan Betular、Gilead Sciences
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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