Recruitment

Recruitment Status
Completed
Estimated Enrollment
186

Inclusion Criterias

Onset of jaundice <3 months prior to Screening
Less than 8 weeks between last intake of alcohol and Screening
Maddrey's Discriminant Function score (DF)>32
...
Onset of jaundice <3 months prior to Screening
Less than 8 weeks between last intake of alcohol and Screening
Maddrey's Discriminant Function score (DF)>32
Willing to provide liver tissue, whole blood, stool and ascitic fluid as part of a correlative study
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
Willing to undergo liver biopsy for histological assessment of alcoholic hepatitis.
Age greater or equal to 18 years

Exclusion Criterias

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
Aspartate aminotransferase (AST) >500 IU/mL; or AST:Alanine aminotransferase (ALT) ratio < 1
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
Aspartate aminotransferase (AST) >500 IU/mL; or AST:Alanine aminotransferase (ALT) ratio < 1
Other clinically significant diseases (uncontrolled diabetes, severe cardiovascular or pulmonary disease, transplant recipient, recent cancer)
Hemoglobin <7g/dL
Pregnant or breast-feeding or unwilling to use appropriate birth control
Use of select contraindicated medications
Renal insufficiency
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)
Laboratory exclusions
Upper GI bleeding requiring transfusion within 48 hours 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))
Liver disease significantly caused by etiologies other than alcohol.
Previous randomization in the trial
Total Bilirubin <7.5mg/dL
Based on the investigators judgment, subject is not capable of complying with the study requirements.

Summary

Conditions
Alcoholic Hepatitis
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

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...

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.

Inclusion Criterias

Onset of jaundice <3 months prior to Screening
Less than 8 weeks between last intake of alcohol and Screening
Maddrey's Discriminant Function score (DF)>32
...
Onset of jaundice <3 months prior to Screening
Less than 8 weeks between last intake of alcohol and Screening
Maddrey's Discriminant Function score (DF)>32
Willing to provide liver tissue, whole blood, stool and ascitic fluid as part of a correlative study
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
Willing to undergo liver biopsy for histological assessment of alcoholic hepatitis.
Age greater or equal to 18 years

Exclusion Criterias

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
Aspartate aminotransferase (AST) >500 IU/mL; or AST:Alanine aminotransferase (ALT) ratio < 1
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
Aspartate aminotransferase (AST) >500 IU/mL; or AST:Alanine aminotransferase (ALT) ratio < 1
Other clinically significant diseases (uncontrolled diabetes, severe cardiovascular or pulmonary disease, transplant recipient, recent cancer)
Hemoglobin <7g/dL
Pregnant or breast-feeding or unwilling to use appropriate birth control
Use of select contraindicated medications
Renal insufficiency
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)
Laboratory exclusions
Upper GI bleeding requiring transfusion within 48 hours 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))
Liver disease significantly caused by etiologies other than alcohol.
Previous randomization in the trial
Total Bilirubin <7.5mg/dL
Based on the investigators judgment, subject is not capable of complying with the study requirements.

Locations

Los Angeles, California, 90033
Torrance, California, 90509
Long Beach, California, 90822
Los Angeles, California, 90033
Torrance, California, 90509
Long Beach, California, 90822

Tracking Information

NCT #
NCT01903798
Collaborators
  • University of Southern California
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • VA Long Beach Healthcare System
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
  • Principal Investigator: Timothy R. Morgan, MD VA Long Beach Healthcare System
  • Timothy R. Morgan, MD VA Long Beach Healthcare System