A Safety and Efficacy Study of Mycophenolate Mofetil and Rilonacept in Patients With Alcoholic Hepatitis

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Southern California Institute for Research and Education; Timothy Morgan, MD
• Collaborators: Los Angeles Biomedical Research Institute; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center; National Institute on Alcohol Abuse and Alcoholism (NIAAA); Southern California Institute for Research and Education; University of Southern California; VA Long Beach Healthcare System
• Treatments: Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Mycophenolate mofetil; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rilonacept

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.