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

NCT01903798 | Completed Phase 2 Results DMC

• 2 other identifiers: SCAHC Clinical Trial1U01AA021886
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

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).

Conditions

Alcoholic Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Patients Reported Ascites

  Week 24

Study Arms (4)

Prednisolone (Lille <0.45)

ACTIVE COMPARATOR

At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.

Drug: Prednisolone

Prednisolone, rilonacept (Lille <0.45)

EXPERIMENTAL

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).

Drug: Prednisolone; Drug: Rilonacept

Prednisolone (Lille >0.45)

ACTIVE COMPARATOR

Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.

Drug: Prednisolone

Prednisolone, mycophenolate(Lille > 0.45)

EXPERIMENTAL

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.

Drug: Mycophenolate mofetil; Drug: Prednisolone

Interventions

Mycophenolate mofetil DRUG

Immunosuppressive agent

Prednisolone, mycophenolate(Lille > 0.45)

Prednisolone DRUG

Corticosteroid

Prednisolone (Lille <0.45); Prednisolone (Lille >0.45); Prednisolone, mycophenolate(Lille > 0.45); Prednisolone, rilonacept (Lille <0.45)

Rilonacept DRUG

Prednisolone, rilonacept (Lille <0.45)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Southern California Institute for Research and Education: lead
• University of Southern California: collaborator
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: collaborator
• VA Long Beach Healthcare System: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (3)

VA Long Beach Healthcare System

Long Beach, California, 90822, United States

Location

LAC USC Medical Center

Los Angeles, California, 90033, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

MeSH Terms

Conditions

Hepatitis, Alcoholic

Interventions

Mycophenolic Acid; Prednisolone; rilonacept

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Executive Director, Southern California Institute for Research and Education
• Organization: SCIRE

Sabry.Eassa@va.gov

562-826-8000

Study Officials

• Timothy R. Morgan, MD

  VA Long Beach Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Hepatology

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 19, 2013
• Study Start: December 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 12, 2025
• Results First Posted: October 25, 2018

Record last verified: 2025-05

Locations

US (3)