Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
研究概览
详细说明
The main study is a Phase 2, double blind, proof-of-concept, randomized study evaluating the safety, tolerability, and biological activity of GS-4997 in combination with prednisolone, compared to prednisolone alone, in subjects with severe, histologically-confirmed AH.
This substudy uses the HepQuant SHUNT Liver Diagnostic test to assess severity of disease at baseline and to track disease progression or improvement over the 24 weeks of the study. The HepQuant SHUNT test will be performed at baseline (Day 1) and at Weeks 1, 2, 4, 12, and 24 regardless of treatment Arm.
GS-4997 Dose and Mode of Administration. Subjects will be randomized 1:1 to either:
- Treatment Group A: GS-4997 18 mg (1 x 18 mg tablet) AND prednisolone 40 mg (4 x 10 mg tablets), both administered orally once daily
- Treatment Group B: GS-4997 placebo (1 tablet) AND prednisolone 40 mg (4 x 10 mg tablets), both administered orally once daily
研究类型
阶段
- 第一阶段早期
联系人和位置
学习地点
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California
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Coronado、California、美国、92118
- Southern California Research Center
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Florida
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Miami、Florida、美国、33136
- University of Miami
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Georgia
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Atlanta、Georgia、美国、30322
- Emory University
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Minnesota
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Minneapolis、Minnesota、美国、55455
- University of Minnesota
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Mississippi
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Jackson、Mississippi、美国、39216
- University of Mississippi Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19104
- University of Pennsylvania
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Texas
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Dallas、Texas、美国、75203
- The Liver Institute At Methodist Dallas Medical Center
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San Antonio、Texas、美国、78215
- American Research Corporation at the Texas Liver Institute
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Utah
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Murray、Utah、美国、84107
- Intermountain Medical Center
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Virginia
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Newport News、Virginia、美国、23602
- Liver Institute of Virginia
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Richmond、Virginia、美国、23226
- Liver Institute of Virginia
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Richmond、Virginia、美国、23298
- VCU Health System
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Washington
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Seattle、Washington、美国、98104
- University of Washington
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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:
- Willing and able to give informed consent prior to any study specific procedures being performed. In individuals with hepatic encephalopathy (HE) which may impair decision-making, consent will be obtained per hospital procedures (eg, by Legally Authorized Representative)
- Clinical diagnosis of severe AH
- Maddrey's DF ≥ 32 at screening
Exclusion Criteria:
Key Exclusion Criteria:
- Pregnant or lactating females;
- Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease;
- Serum AST >400 U/L or ALT >300 U/L;
- MELD >30 at screening;
- Maddrey's DF >60 at screening;
- Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
- Concomitant or previous history of hepatocellular carcinoma;
- History of liver transplantation;
- HIV Ab positive;
- Clinical suspicion of pneumonia;
- Uncontrolled sepsis;
- Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood;
- Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine >221 μmol/L (>2.5 mg/dL) or the requirement for renal replacement therapy;
- Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
- Portal vein thrombosis;
- Acute pancreatitis;
- Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
学习计划
研究是如何设计的?
设计细节
- 主要用途:诊断
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:GS-4997 + Prednisolone
GS-4997 + Prednisolone for 28 days HepQuant SHUNT Test |
Experimental drug
Control drug that is also administered with the Experimental drug, GS-4997.
This drug is used in both arms.
The HepQuant SHUNT Liver Diagnostic Kit is intended for use in the quantitative detection of 13C-cholate and d4-cholate in blood serum, collected after the intravenous administration of 13C-cholate and the oral ingestion of d4-cholate. The device is indicated to assess the severity of liver disease. For use by health care professionals. Administer the test under a physician's supervision. The HepQuant Analytical Testing Laboratory must analyze the serum samples.
其他名称:
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安慰剂比较:Prednisolone + Placebo
Placebo + Prednisolone for 28 days HepQuant SHUNT Test |
安慰剂
Control drug that is also administered with the Experimental drug, GS-4997.
This drug is used in both arms.
The HepQuant SHUNT Liver Diagnostic Kit is intended for use in the quantitative detection of 13C-cholate and d4-cholate in blood serum, collected after the intravenous administration of 13C-cholate and the oral ingestion of d4-cholate. The device is indicated to assess the severity of liver disease. For use by health care professionals. Administer the test under a physician's supervision. The HepQuant Analytical Testing Laboratory must analyze the serum samples.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
大体时间:HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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Using the SHUNT DSI to evaluate the liver, this outcome will compare the two arms to determine if SHUNT DSI is able to measure a change between the experimental and control groups.
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HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Secondary Outcome 1
大体时间:HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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To determine the relationship of baseline Disease Severity Index (DSI) to mortality risk;
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HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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Secondary Outcome 2
大体时间:HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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To determine the relationship of change in Disease Severity Index (DSI) to mortality risk
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HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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Secondary Outcome 3
大体时间:HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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To correlate baseline Disease Severity Index (DSI) with baseline Maddrey, MELD, and Lille scorestest with the pharmacokinetics of GS-4997
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HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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Secondary Outcome 4
大体时间:HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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To determine the relationship between baseline Disease Severity Index (DSI), Maddrey, MELD, and Lille scores and mortality
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HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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合作者和调查者
调查人员
- 首席研究员:Greg Everson, MD、HepQuant, LLC
研究记录日期
研究主要日期
学习开始 (预期的)
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 (实际的)
研究记录更新
最后更新发布 (实际的)
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.
安慰剂的临床试验
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City of Hope Medical CenterNational Cancer Institute (NCI)主动,不招人造血和淋巴细胞肿瘤 | 骨髓纤维化 | 慢性淋巴细胞白血病 | 缓解期成人急性髓性白血病 | 骨髓增生异常综合症 | 缓解期成人急性淋巴细胞白血病 | 骨髓增殖性肿瘤 | 慢性期慢性粒细胞白血病,BCR-ABL1 阳性 | 成人淋巴母细胞淋巴瘤 | 加速期慢性粒细胞白血病,BCR-ABL1 阳性 | HLA-A*0201 阳性细胞存在 | 巨细胞病毒感染 | 成人霍奇金淋巴瘤 | 成人非霍奇金淋巴瘤美国
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Mila (bMotion Technologies)完全的
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Universidad Autonoma de MadridCentro Universitario La Salle完全的