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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by Southern California Institute for Research and Education
Sponsor:
Collaborators:
LA County - USC Medical Center
University of California, Los Angeles
VA Long Beach Healthcare System
Information provided by (Responsible Party):
Timothy Morgan, MD, Southern California Institute for Research and Education
ClinicalTrials.gov Identifier:
NCT01903798
First received: July 16, 2013
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

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).


Condition Intervention Phase
Alcoholic Hepatitis
Drug: Rilonacept
Drug: Mycophenolate mofetil
Drug: Prednisolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Southern California Institute for Research and Education:

Primary Outcome Measures:
  • Survival [ Time Frame: Day 8 to Day 29 ] [ Designated as safety issue: Yes ]
    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.

  • Change in Bilirubin [ Time Frame: Day 8 to Day 29 ] [ Designated as safety issue: Yes ]
    To determine whether treatment with prednisolone and rilonacept (Arcalyst®) (anti-interleukin-1 [IL-1]) is better than treatment with prednisolone (standard of care) among patients with alcoholic hepatitis who respond to 1 week of prednisolone (i.e., Lille score of <0.45). Primary outcome is change in bilirubin between Day 8 (start of treatment) and Day 29 (end of treatment).


Secondary Outcome Measures:
  • Safety [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    To determine adverse events, especially infection and renal failure, for each treatment group.

  • MELD and DF Score [ Time Frame: Day 8 to Day 29 ] [ Designated as safety issue: No ]
    To determine the change in MELD score and in Maddrey's discriminant function between Day 8 and Day 29 for each treatment group.


Estimated Enrollment: 186
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Continue Prednisolone (Lille <0.45)
Continue prednisolone 40 mg/day (current standard of care) for 21 days.
Drug: Prednisolone
Corticosteroid
Experimental: Rilonacept + Prednisolone (Lille <0.45)
Prednisolone (40mg/day) and rilonacept (Arcalyst®) subcutaneously once a week for 21 days (320 mg on study Day 8 and 160 mg on study Day 15 and study Day 22).
Drug: Rilonacept
Interleukin-1 blocker
Other Name: ARCALYST®
Drug: Prednisolone
Corticosteroid
No Intervention: Standard of Care (Lille ≥ 0.45)
Standard of care therapy (continue prednisolone, stop all therapy and/or offer palliative care)
Experimental: Mycophenolate + Prednisolone (Lille ≥ 0.45)
Prednisolone (40 mg/day) and mycophenolate mofetil for 21 days (500 mg BID for first 4 days followed by 1000 mg BID for the next 17 days).
Drug: Mycophenolate mofetil
Immunosuppressive agent
Other Name: CellCept®
Drug: Prednisolone
Corticosteroid

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01903798

Contacts
Contact: Aliya Asghar, MPH 562-826-5212 aliya.asghar@va.gov

Locations
United States, California
VA Long Beach Healthcare System Not yet recruiting
Long Beach, California, United States, 90822
Contact: Aliya Asghar, MPH    562-826-5212    aliya.asghar@va.gov   
Principal Investigator: Timothy R. Morgan, MD         
Sub-Investigator: Robert H. Lee, MD, MAS         
LAC USC Medical Center Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Susan Milstein, RN, BSN    323-226-4727    smilstei@med.usc.edu   
Principal Investigator: Andrew Stolz, MD         
Sub-Investigator: Neil Kaplowitz, MD         
Harbor-UCLA Medical Center Not yet recruiting
Torrance, California, United States, 90509
Contact: John Tayek, MD    310-222-1237    jtayek@dhs.lacounty.gov   
Principal Investigator: John Tayek, MD         
Sponsors and Collaborators
Timothy Morgan, MD
LA County - USC Medical Center
University of California, Los Angeles
VA Long Beach Healthcare System
Investigators
Principal Investigator: Timothy R. Morgan, MD VA Long Beach Healthcare System/Southern California Institute for Research and Education
  More Information

No publications provided

Responsible Party: Timothy Morgan, MD, Chief, Hepatology, Southern California Institute for Research and Education
ClinicalTrials.gov Identifier: NCT01903798     History of Changes
Other Study ID Numbers: SCAHC Clinical Trial, 1U01AA021886
Study First Received: July 16, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 28, 2014