A Phase II, Multicenter, Randomized, Open-label Study to Investigate the Safety and Efficacy of Mycophenolate Mofetil and Rilonacept (Anti-interleukin-1) in Patients With Alcoholic Hepatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 3
- 主要终点
- Survival at Day 29 of the Assigned Treatment
研究概览
简要总结
This clinical trial will test two new therapies for the treatment of alcoholic hepatitis. Patients who "respond" to the current standard of care therapy for alcoholic hepatitis(corticosteroid/prednisolone therapy) after 1 week of treatment will be randomly assigned to either continue on standard therapy, or, to begin treatment with rilonacept in combination with standard therapy. Patients who are "non-responders" to the current standard of care therapy after 1 week of treatment will be randomly assigned to standard of care or to begin treatment with mycophenolate mofetil in combination with standard therapy. Patients will be treated for a total of 4 weeks in this clinical trial. Patients will be followed for up to five months after completing therapy (6 months total).
详细描述
This is a prospective, randomized trial of two experimental treatments, prednisolone + mycophenolate mofetil and prednisolone + rilonacept, in comparison with standard of care, in patients with alcoholic hepatitis. Patients will start therapy with prednisolone. At Day 8 response to prednisolone will be determined using the Lille score. Patients with a Lille score ≥ 0.45 will be randomized to standard of care (continue prednisolone, stop all therapy and/or offer palliative care) or to have prednisolone continued and mycophenolate added for the next three weeks. Patients with a Lille score <0.45 will be randomized to continue prednisolone alone (standard of care) or to have rilonacept added to their treatment regimen (experimental group) for the next three weeks. Patients will complete follow-up visits at Week 12 and Week 24.
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
- •History of chronic alcohol consumption (defined as >60g ethanol/day for women and >80g ethanol/day for men) for at least the past 5 years
- •Less than 8 weeks between last intake of alcohol and Screening
- •Maddrey's Discriminant Function score (DF)>32
- •Willing to undergo liver biopsy for histological assessment of alcoholic hepatitis.
- •Willing to provide liver tissue, whole blood, stool and ascitic fluid as part of a correlative study
- •Onset of jaundice <3 months prior to Screening
- •Age greater or equal to 18 years
- •Exclusion Criteria (Brief):
- •Liver disease significantly caused by etiologies other than alcohol.
- •Upper GI bleeding requiring transfusion within 48 hours prior to start of prednisolone (Day 1)
- •Infection that has been treated with appropriate antibiotics for less than 72 hours or which has not responded appropriately to 72 hours or more of antibiotic treatment prior to start of prednisolone (Day 1)
- •Clinical evidence of select active infections in the past 3 months (fungal, mycobacterial, cytomegalovirus (CMV), herpes, coccidioidomycosis, tuberculosis (TB) and human immunodeficiency virus (HIV))
- •Renal insufficiency
- •Laboratory exclusions
- •Hemoglobin <7g/dL
- •Total Bilirubin <7.5mg/dL
- •Aspartate aminotransferase (AST) >500 IU/mL; or AST:Alanine aminotransferase (ALT) ratio < 1
- •Pregnant or breast-feeding or unwilling to use appropriate birth control
- •Other clinically significant diseases (uncontrolled diabetes, severe cardiovascular or pulmonary disease, transplant recipient, recent cancer)
- •Use of oral or systemic corticosteroids for more than 7 days during the 14 days prior to Day 1 or likely use of oral or systemic corticosteroids in the first 12 weeks of the clinical trial for underlying diseases
- •Use of select contraindicated medications
- •Previous randomization in the trial
- •Based on the investigators judgment, subject is not capable of complying with the study requirements.
排除标准
- 未提供
研究组 & 干预措施
Prednisolone (Lille <0.45)
At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.
干预措施: Prednisolone (Drug)
Prednisolone, rilonacept (Lille <0.45)
This group will continue Prednisolone (40mg/day). Additionally, they will receive rilonacept (Arcalyst®) once a week for 21 days. After randomization at Day 8, study participants will be given 320 mg subcutaneously (two injections of 2.0 ml, 160 mg each). On Day 15 and Day 22, study participants will be given 160 mg subcutaneously (one injection of 160 mg).
干预措施: Prednisolone (Drug)
Prednisolone, rilonacept (Lille <0.45)
This group will continue Prednisolone (40mg/day). Additionally, they will receive rilonacept (Arcalyst®) once a week for 21 days. After randomization at Day 8, study participants will be given 320 mg subcutaneously (two injections of 2.0 ml, 160 mg each). On Day 15 and Day 22, study participants will be given 160 mg subcutaneously (one injection of 160 mg).
干预措施: Rilonacept (Drug)
Prednisolone (Lille >0.45)
Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.
干预措施: Prednisolone (Drug)
Prednisolone, mycophenolate(Lille > 0.45)
This group will continue Prednisolone (40mg/day). Additionally, they will receive mycophenolate mofetil (CellCept®) for a total of 21 days. After randomization at Day 8, they will receive CellCept® at a dose of 1000 mg per day for the first four days followed by 2000 mg per day (two 500 mg tablets bid) for the remaining 17 days.
干预措施: Mycophenolate mofetil (Drug)
Prednisolone, mycophenolate(Lille > 0.45)
This group will continue Prednisolone (40mg/day). Additionally, they will receive mycophenolate mofetil (CellCept®) for a total of 21 days. After randomization at Day 8, they will receive CellCept® at a dose of 1000 mg per day for the first four days followed by 2000 mg per day (two 500 mg tablets bid) for the remaining 17 days.
干预措施: Prednisolone (Drug)
结局指标
主要结局
Survival at Day 29 of the Assigned Treatment
时间窗: Day 8 to Day 29
To determine whether treatment with prednisolone + mycophenolate mofetil is better than standard of care treatment among patients with alcoholic hepatitis who fail to respond to 1 week of prednisolone (i.e., Lille score of ≥0.45). Primary outcome is survival at Day 29. All study participants received the Standard of care (prednisolone) with or without experimental drug at Day 1 (based on randomization). Response to the treatment was determined at Day 8. Data was collected for both responders and non-responders.
次要结局
- Number of Patients Reported Ascites(Week 24)
研究者
Timothy Morgan, MD
Chief, Hepatology
Southern California Institute for Research and Education