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

Phase 2

Completed

Conditions: Alcoholic Hepatitis

Interventions: Drug: Prednisolone
Drug: Mycophenolate mofetil
Drug: Rilonacept

Registration Number: NCT01903798

Lead Sponsor: Southern California Institute for Research and Education

Brief 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).

Detailed 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 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prednisolone, rilonacept (Lille <0.45)	Rilonacept	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 (Lille <0.45)	Prednisolone	At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.
Prednisolone, mycophenolate(Lille <0.45)	Mycophenolate mofetil	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.
Prednisolone, rilonacept (Lille <0.45)	Prednisolone	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 (Lille >0.45)	Prednisolone	Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.
Prednisolone, mycophenolate(Lille <0.45)	Prednisolone	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.

Primary Outcome Measures

Name	Time	Method
Survival at Day 29 of the Assigned Treatment	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Reported Ascites	Week 24

Trial Locations

Locations (3): LAC USC Medical Center
🇺🇸
Los Angeles, California, United States
Harbor-UCLA Medical Center
🇺🇸
Torrance, California, United States
VA Long Beach Healthcare System
🇺🇸
Long Beach, California, United States