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

December 26, 2018 updated by: Timothy Morgan, MD, Southern California Institute for Research and Education

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Long Beach, California, United States, 90822
        • VA Long Beach Healthcare System
      • Los Angeles, California, United States, 90033
        • LAC USC Medical Center
      • Torrance, California, United States, 90509
        • Harbor-UCLA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Prednisolone (Lille <0.45)
At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.
Drug: Prednisolone
Corticosteroid
Experimental: Prednisolone, rilonacept (Lille <0.45)
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: Rilonacept
Drug: Prednisolone
Corticosteroid
Active Comparator: Prednisolone (Lille >0.45)
Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.
Drug: Prednisolone
Corticosteroid
Experimental: Prednisolone, mycophenolate(Lille <0.45)
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: Prednisolone
Corticosteroid
Drug: Mycophenolate mofetil
Immunosuppressive agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival at Day 29 of the Assigned Treatment
Time Frame: 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.
Day 8 to Day 29

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Patients Reported Ascites
Time Frame: Week 24
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southern California Institute for Research and Education

Collaborators

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

Investigators

  • Principal Investigator: Timothy R. Morgan, MD, VA Long Beach Healthcare System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

July 16, 2013

First Submitted That Met QC Criteria

July 16, 2013

First Posted (Estimate)

July 19, 2013

Study Record Updates

Last Update Posted (Actual)

January 14, 2019

Last Update Submitted That Met QC Criteria

December 26, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCAHC Clinical Trial
  • 1U01AA021886 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcoholic Hepatitis

Clinical Trials on Rilonacept

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe