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

Primary Purpose

Alcoholic Hepatitis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Mycophenolate mofetil
Prednisolone
Rilonacept
Sponsored by
Southern California Institute for Research and Education
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • VA Long Beach Healthcare System
  • LAC USC Medical Center
  • Harbor-UCLA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Prednisolone (Lille <0.45)

Prednisolone, rilonacept (Lille <0.45)

Prednisolone (Lille >0.45)

Prednisolone, mycophenolate(Lille <0.45)

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Patients Reported Ascites

Full Information

First Posted
July 16, 2013
Last Updated
December 26, 2018
Sponsor
Southern California Institute for Research and Education
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)
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1. Study Identification

Unique Protocol Identification Number
NCT01903798
Brief Title
A Safety and Efficacy Study of Mycophenolate Mofetil and Rilonacept in Patients With Alcoholic Hepatitis
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Southern California Institute for Research and Education
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)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prednisolone (Lille <0.45)
Arm Type
Active Comparator
Arm Description
At Day 8, after randomization, this participants will continue prednisolone 40 mg/day (current standard of care) for 21 days.
Arm Title
Prednisolone, rilonacept (Lille <0.45)
Arm Type
Experimental
Arm Description
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).
Arm Title
Prednisolone (Lille >0.45)
Arm Type
Active Comparator
Arm Description
Prednisolone (40 mg/day) for the first 7 days, after randomization at Day 8, they will stop all therapy.
Arm Title
Prednisolone, mycophenolate(Lille <0.45)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Intervention Description
Immunosuppressive agent
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Corticosteroid
Intervention Type
Drug
Intervention Name(s)
Rilonacept
Primary Outcome Measure Information:
Title
Survival at Day 29 of the Assigned Treatment
Description
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.
Time Frame
Day 8 to Day 29
Secondary Outcome Measure Information:
Title
Number of Patients Reported Ascites
Time Frame
Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy R. Morgan, MD
Organizational Affiliation
VA Long Beach Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Long Beach Healthcare System
City
Long Beach
State/Province
California
ZIP/Postal Code
90822
Country
United States
Facility Name
LAC USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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