Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 12
- 主要终点
- To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
研究概览
简要总结
This clinical investigation is a substudy within GS-US-416-2124, IND 129570, which is A Phase 2, Double-Blind, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 in Combination with Prednisolone versus Prednisolone Alone in Subjects with Severe Alcoholic Hepatitis. The use of the HepQuant SHUNT test is to assess liver disease severity before, during, and after treatment with GS-4997 or placebo, to assess liver disease severity.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Care Provider)
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
- •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
排除标准
- •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.
研究组 & 干预措施
GS-4997 + Prednisolone
GS-4997 + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: GS-4997 (Drug)
GS-4997 + Prednisolone
GS-4997 + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: Prednisolone (Drug)
GS-4997 + Prednisolone
GS-4997 + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: HepQuant SHUNT Test (Device)
Prednisolone + Placebo
Placebo + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: Prednisolone (Drug)
Prednisolone + Placebo
Placebo + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: HepQuant SHUNT Test (Device)
Prednisolone + Placebo
Placebo + Prednisolone for 28 days
HepQuant SHUNT Test
干预措施: Placebo (Drug)
结局指标
主要结局
To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
时间窗: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
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.
次要结局
- Secondary Outcome 1(HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24)
- Secondary Outcome 2(HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24)
- Secondary Outcome 3(HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24)
- Secondary Outcome 4(HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24)