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

Alcoholic Hepatitis Clinical Trial

Official title:

A Phase II, Multicenter, Randomized, Open-label Study to Investigate the Safety and Efficacy of Mycophenolate Mofetil and Rilonacept (Anti-interleukin-1) in Patients With Alcoholic Hepatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903798
• Other study ID #: SCAHC Clinical Trial
• Secondary ID: 1U01AA021886
• Status: Completed
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: April 2016

Study information

• Verified date: October 2018
• Source: Southern California Institute for Research and Education
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• Mycophenolate mofetil
Immunosuppressive agent
• Prednisolone
Corticosteroid
• Rilonacept

Locations

Country	Name	City	State
United States	VA Long Beach Healthcare System	Long Beach	California
United States	LAC USC Medical Center	Los Angeles	California
United States	Harbor-UCLA Medical Center	Torrance	California

Sponsors (5)

Lead Sponsor	Collaborator
Southern California Institute for Research and Education	Los Angeles Biomedical Research Institute, National Institute on Alcohol Abuse and Alcoholism (NIAAA), University of Southern California, VA Long Beach Healthcare System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at Day 29 of the Assigned Treatment	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.	Day 8 to Day 29
Secondary	Number of Patients Reported Ascites		Week 24