NCT02854631已完成2 期
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 (AH)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 44
- 主要终点
- Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of selonsertib (GS-4997) in combination with prednisolone versus prednisolone alone in participants with severe alcoholic hepatitis (AH).
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
- Double (Participant, Investigator)
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 Discriminant Function (DF) ≥ 32 at screening
排除标准
- •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 aspartate aminotransferase (AST) >400 U/L or alanine aminotransferase (ALT) >300 U/L;
- •Model for End Stage Liver Disease (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
Selonsertib + Prednisolone
Experimental
Selonsertib + prednisolone for 28 days
干预措施: Selonsertib (Drug)
Selonsertib + Prednisolone
Experimental
Selonsertib + prednisolone for 28 days
干预措施: Prednisolone (Drug)
Prednisolone
Placebo Comparator
Selonsertib placebo + prednisolone for 28 days
干预措施: Prednisolone (Drug)
Prednisolone
Placebo Comparator
Selonsertib placebo + prednisolone for 28 days
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
时间窗: Up to Day 28 plus 30 days
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
次要结局
- Percentage of Participants Who Died by Day 28(Day 28)
- Percentage of Participants With Survival at Day 28 Using Kaplan-Meier(Day 28)
- Percentage of Participants With Survival at Week 8 Using Kaplan-Meier(Week 8)
- Percentage of Participants With Survival at Week 12 Using Kaplan-Meier(Week 12)
- Percentage of Participants Who Died by Week 8(Week 8)
- Percentage of Participants Who Died by Week 12(Week 12)
- Percentage of Participants Who Died by Week 24(Week 24)
- Percentage of Participants With Survival at Week 24 Using Kaplan-Meier(Week 24)
- Percentage of Participants Who Received a Liver Transplant(Day 28, Week 8, Week 12, and Week 24)
- Percentage of Participants With Hepatorenal Syndrome (HRS)(Up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase(Baseline (Day 1) and up to 24 weeks)
- Percentage of Participants With Infection(Up to 24 weeks)
- Length of Hospital Stay(Up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT)(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST)(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT)(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Bilirubin(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: Albumin(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR)(Baseline (Day 1) and up to 24 weeks)
- Percentage of Participants With Lille Response (Score < 0.45) at Day 7(Day 7)
- Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7(Day 7)
- Lille Score at Day 7 as a Continuous Variable(Day 7)
- Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score(Baseline and Day 7 Time Points used to calculate Overall Mortality Risk at Months 2 and 6)
- Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score(Baseline (Day 1) and up to 24 weeks)
- Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score(Baseline (Day 1) and up to 24 weeks)
研究者
研究点 (44)
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