A Safety and Efficacy Study of Mycophenolate Mofetil and Rilonacept 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).
Drug: Mycophenolate mofetil
|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|
- 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).
- 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 Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Continue Prednisolone (Lille <0.45)
Continue prednisolone 40 mg/day (current standard of care) for 21 days.
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).
Other Name: ARCALYST®Drug: Prednisolone
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
Other Name: CellCept®Drug: Prednisolone
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.
|Contact: Aliya Asghar, MPHfirstname.lastname@example.org|
|United States, California|
|VA Long Beach Healthcare System||Not yet recruiting|
|Long Beach, California, United States, 90822|
|Contact: Aliya Asghar, MPH 562-826-5212 email@example.com|
|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 firstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator: John Tayek, MD|
|Principal Investigator:||Timothy R. Morgan, MD||VA Long Beach Healthcare System/Southern California Institute for Research and Education|