Integrated alcohol‑use and liver treatments for severe alcohol‑associated hepatitis

Integrated Therapies for Alcohol Use in Alcohol-associated Liver Disease (ITAALD) Trial

This trial tests whether adding medication (acamprosate) plus counseling for alcohol use disorder to liver therapy helps people with severe alcohol‑associated hepatitis drink less and have better liver outcomes at six months, and also compares a new drug (F‑652) to prednisone for short‑term survival.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 216 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Indiana University (Academic / other)
• Drugs / interventions: prednisone
• Locations: 6 sites (Indianapolis, Indiana and 5 other locations)
• Trial ID: NCT07060638 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double‑blind, placebo‑controlled Phase 2 trial using a sequentially randomized design in 216 patients with severe alcohol‑associated hepatitis (sAH). Patients receive either IL‑22 (F‑652) or prednisone for sAH, and survivors at Day 7 are randomized to receive an AUD intervention (acamprosate plus motivational interviewing/enhancement therapy) or usual care (brief advice and 12‑step referral). The primary endpoint is a composite of alcohol‑ and liver‑related events at six months; secondary endpoints include 90‑day survival comparing F‑652 versus prednisone using the Day‑7 Lille score as a stopping rule and one‑year overall survival. The trial is conducted at multiple U.S. academic centers selected by NIAAA and uses standard eligibility criteria for severe AH including MELD 20–35 and recent onset of jaundice.

Who should consider this trial

Good fit: Adults 18–69 hospitalized with severe alcohol‑associated hepatitis (MELD 20–35), recent onset of jaundice within 8 weeks, ongoing heavy alcohol use meeting NIAAA criteria, and meeting the trial's laboratory or biopsy confirmation rules are ideal candidates.

Not a fit: Patients with milder liver disease, age over 70, competing causes of liver injury, or those who die within the first seven days of illness are unlikely to receive benefit from the AUD intervention portion of the trial.

Why it matters

Potential benefit: If successful, the integrated approach could reduce alcohol relapse, lower liver‑related complications, and improve survival for people with severe alcohol‑associated hepatitis.

How similar studies have performed: Acamprosate and counseling are established treatments for alcohol use disorder and prednisone has shown modest benefit in severe alcoholic hepatitis, but IL‑22 (F‑652) and the integrated sAH+AUD treatment approach are novel and not yet proven.

Eligibility criteria

Inclusion Criteria

* Age ≥18, \<70
* MELD 20-35 on day of randomization
* Definitive or probable diagnosis as defined by the NIAAA criteria
* Onset of jaundice (defined as serum total bilirubin \>3 mg/dL) within the prior 8 weeks
* Ongoing 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
* AST \> 50 IU/L,
* AST: ALT \> 1.5
* ALT and AST values \< 400 IU/L
* and/or histological evidence of AH\*

  \*In patients with possible AH or AH with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g., patient denies excessive alcohol use), and atypical/abnormal laboratory tests (e.g., AST \< 50 IU/L or \> 400 IU/L, AST/ALT ratio \< 1.5), antinuclear antibody \> 1:160 or SMA \> 1:80, a standard of care liver biopsy may be performed during current hospital admission to confirm AH and exclude competing etiologies.
* Females of childbearing (reproductive) potential must have a negative serum or urine pregnancy test at screening.

Exclusion Criteria

* Active listing for liver transplantation before screening
* MELD score \<20 or \> 35
* Uncontrolled infection (persistent positive blood or other body fluid cultures despite 48 hours of antibiotic therapy)
* Progressive hemodynamic compromise requiring intravenous pressors
* Pneumonia as evidenced by clinical and radiological examination
* Renal failure defined by estimated GFR \<35 mL/min.
* Clinically active C. diff infection
* Evidence of other liver diseases (such as autoimmune hepatitis, primary biliary cholangiopathy, primary sclerosing cholangitis, ischemic, sepsis- or drug-induced liver disease)
* History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer
* Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 2 days within the previous 30 days
* Current use of naltrexone or acamprosate.
* Clinically significant pancreatitis- abdominal pain, elevated lipase (\> 3 X ULN), and at least edema of pancreas with fat-stranding on CT scan
* Active gastrointestinal bleeding defined as hematemesis or melena with a decrease in hemoglobin more than 2 g/dl in 24 hours due to gastrointestinal bleeding, or with a decrease in mean arterial BP to \< 65 mmHg
* Significant concomitant medical illnesses (such as uncontrolled congestive heart failure or COPD or progressive multi-organ failure) as determined by the study investigator
* Uncontrolled mental illness as determined by the study investigator
* Uncontrolled HBV, HIV, or HCV infection with persistent viremia. However, subjects with controlled (undetectable viral load) HIV and HBV on viral suppressive therapies will be enrolled and subjects with history of HCV will be enrolled if they have evidence of SVR one year prior to enrollment
* Active illicit opiates, cocaine, ketamine, or methamphetamine use in the last 30 days.
* Uncontrolled diabetes mellitus with A1c \> 9
* Pregnancy or breastfeeding
* Known allergy or intolerance to therapeutic agents to be tested
* Unwillingness to stop alcohol use and to undergo AUD treatment
* Unwillingness to either abstain from sexual intercourse, or if sexually active, use a reliable method of birth control during the study and for at least 30 days after the last dose of the study medication. Examples of acceptable birth control methods include double barrier method such as condom and occlusive cap (diaphragm or cervical cap) with spermicidal foam/gel/film/cream/suppository; birth control pills, patches, injections, or implants; intrauterine device (IUD); vasectomy and tubal ligation.
* Participant has any condition or circumstance that adversely affects the participant, could cause noncompliance with treatment or visits, may impact the interpretation of clinical data, could cause bias, or may otherwise contraindicate the participant's participation in the study.

Where this trial is running

Indianapolis, Indiana and 5 other locations

• Indiana University — Indianapolis, Indiana, United States (Recruiting)
• University of Louisville — Louisville, Kentucky, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• University of Texas Southwestern Medical School — Dallas, Texas, United States (Recruiting)
• Virginia Commonwealth University — Richmond, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Savannah Yarnelle

Conditions Alcohol-associated Hepatitis; Severe AH, AUD