Samer Gawrieh
This is a multicenter, randomized, double-blinded, placebo-controlled trial focused on the treatment of severe alcohol-associated hepatitis (sAH) and alcohol use disorder (AUD). The primary purpose of the study is to determine whether subjects receiving sAH therapy in addition to AUD treatments will have better alcohol and liver-related outcomes at 6 months compared to sAH therapy plus usual care for AUD. Patients assigned to the AUD treatment will receive Acamprosate and counseling whereas those assigned to AUD standard care will receive brief advice and referral to a 12-step program. The secondary purpose of the study is to determine if F-652 is safe and effective in treating sAH when compared to prednisone. Subjects will receive F-652 on days 1 and 7 or prednisone for 28 days. Outcomes will be measured by overall survival at 90 days.
Objectives: 1. To determine whether interventions directed to treat AUD integrated with sAH therapies will improve a composite endpoint of alcohol and liver-related events at 6 months compared to usual care for AUD (primary endpoint). 2. To compare 90-day survival in patients receiving F-652 with those receiving up to 28 days of prednisone using the Day-7 Lille score as a stopping rule (secondary endpoint). 3. To compare one-year overall survival in patients receiving either IL-22 or prednisone with or without acamprosate (secondary endpoint). Trial design and conduct The Investigators will…
Inclusion Criteria 1. Age ≥18, \<70 2. MELD 20-35 3. Definitive or probable diagnosis of sAH as defined by the NIAAA criteria4, 5 A. Onset of jaundice (defined as serum total bilirubin \>3 mg/dL) within the prior 8 weeks B. Ongoing average consumption of \> 40 gm (for females) and \> 60 gm (for males) alcohol daily for 6 months or more with less than 8 weeks of abstinence before onset of jaundice; OR If, in the investigator's judgment, alcohol use may have been underreported, available clinical evidence-including collateral history, medical records, prior documentation of alcohol use, alcohol…
F-652 (IL-22) is a fusion protein of human IL-22 with IgG2 fragment, and has anti-inflammatory effects
Prednisone is an adrenal glucocorticoid with anti-inflammatory effects
Acamprosate is a propane-1 sulfonic acid with anti-ethanol dependency effects
Matching placebo
Matching Placebo
MI is an evidence-based counseling style to overcome ambivalence to treatment in AUD patients
MET is an MI-based approach that includes 2-4 behavioral treatment sessions based on the Platform Treatment Manual
defined as a brief intervention with advice not to drink alcohol-containing beverages and referral to a 12-step program