A Safety and Efficacy Study of Mycophenolate Mofetil and Rilonacept in Patients With Alcoholic Hepatitis
Alcoholic Hepatitis
About this trial
This is an interventional treatment trial for Alcoholic Hepatitis
Eligibility Criteria
Inclusion Criteria:
- 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.
Sites / Locations
- VA Long Beach Healthcare System
- LAC USC Medical Center
- Harbor-UCLA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Active Comparator
Experimental
Prednisolone (Lille <0.45)
Prednisolone, rilonacept (Lille <0.45)
Prednisolone (Lille >0.45)
Prednisolone, mycophenolate(Lille <0.45)
At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.
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).
Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.
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.