Clinical trial NCT01903798: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Lead sponsor: Southern California Institute for Research and Education
Sponsor class: OTHER
Collaborators: name: University of Southern California
name: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: VA Long Beach Healthcare System
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2013-07-19
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Survival at Day 29 of the Assigned Treatment
timeFrame: Day 8 to Day 29
Secondary outcomes:
measure: Number of Patients Reported Ascites
timeFrame: Week 24
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Los Angeles
country: United States
facility: LAC USC Medical Center
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
Study officials:
affiliation: VA Long Beach Healthcare System
name: Timothy R. Morgan, MD
role: PRINCIPAL_INVESTIGATOR
References: