A Safety and Efficacy Study of Mycophenolate Mofetil and Rilonacept in Patients With Alcoholic Hepatitis
Condition: Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Intervention: Mycophenolate mofetil; Prednisolone; Rilonacept
Intervention description: Immunosuppressive agent; Corticosteroid
Intervention MeSH terms: Mycophenolic Acid; Prednisolone; Rilonacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

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.