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

NCT07060638 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ITAALDU24AA026969
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Alcohol-associated Hepatitis

Keywords

Severe AH, AUD

Outcome Measures

Primary Outcomes (8)

• Death

  Number (%) of participants who die from any cause

  6 months

• Liver transplant

  Number (%) of participants who receive liver transplant

  6 months

• Ascites

  Number (%) of participants with new onset of clinically detectable

  6 months

• Hepatic encephalopathy

  Number (%) of participants with hepatic encephalopathy ≥ New Haven grade 2

  6 months

• Portal hypertensive bleeding

  Number (%) of participants with gastroesophageal varices or portal gastropathy

  6 months

• Liver-related hospital admission

  Number (%) of participants with liver-related hospital admission for ascites, hepatic encephalopathy, infection, GI bleeding

  6 months

• Increase in MELD score > 5 points

  Number (%) of participants with increase in MELD score \> 5 points

  6 months

• Return to drinking

  Number (%) of participants that return to drinking defined as \<100% abstinence-using timeline follow back questionnaire

  6 months

Secondary Outcomes (1)

• Transplant-free survival

  30 days, 90 days, 180 days, 1 year, and 2 years

Other Outcomes (5)

• Change in MELD Score

  30, 90, 180 days

• Acute kidney injury (AKI)

  30, 90, 180 days

• Multi-organ failure

  30, 90, 180 days

Study Arms (4)

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET

ACTIVE COMPARATOR

F-652 on days 1 and 7 and matching placebos for prednisone for 28 days and acamprosate for 6 months. MI will be delivered during the hospitalization; MET sessions will be delivered in the first 3 months

Drug: IL-22; Drug: Acamprosate; Drug: Prednisone placebo; Behavioral: Motivational Interviewing (MI); Behavioral: Motivational Enhancement Therapy (MET)

IL-22 (F-652), Prednisone Placebo, and usual care

ACTIVE COMPARATOR

F-652 on days 1 and 7 and matching placebo for prednisone for 28 days and usual care for AUD.

Drug: IL-22; Drug: Prednisone placebo; Behavioral: Usual Care

Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET

ACTIVE COMPARATOR

Prednisone for 28 days and matching placebos for F-652 on days 1 and 7 and acamprosate for 6 months. MI will be delivered during the hospitalization; MET sessions will be delivered in the first 3 months

Drug: Prednisone; Drug: Acamprosate; Drug: IL-22 (F-652) Placebo; Behavioral: Motivational Interviewing (MI); Behavioral: Motivational Enhancement Therapy (MET)

Prednisone, IL-22 (F-652) Placebo, and usual care

ACTIVE COMPARATOR

Prednisone for 28 days and matching placebo for F-652 on days 1 and 7 and usual care for AUD.

Drug: Prednisone; Drug: IL-22 (F-652) Placebo; Behavioral: Usual Care

Interventions

IL-22 DRUG

F-652 (IL-22) is a fusion protein of human IL-22 with IgG2 fragment, and has anti-inflammatory effects

Also known as: F-652

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET; IL-22 (F-652), Prednisone Placebo, and usual care

Prednisone DRUG

Prednisone is an adrenal glucocorticoid with anti-inflammatory effects

Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET; Prednisone, IL-22 (F-652) Placebo, and usual care

Acamprosate DRUG

Acamprosate is a propane-1 sulfonic acid with anti-ethanol dependency effects

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET; Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET

Prednisone placebo DRUG

Matching placebo

Also known as: Placebo

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET; IL-22 (F-652), Prednisone Placebo, and usual care

IL-22 (F-652) Placebo DRUG

Matching Placebo

Also known as: Placebo

Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET; Prednisone, IL-22 (F-652) Placebo, and usual care

Motivational Interviewing (MI) BEHAVIORAL

MI is an evidence-based counseling style to overcome ambivalence to treatment in AUD patients

Also known as: Behavioral therapy

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET; Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET

Motivational Enhancement Therapy (MET) BEHAVIORAL

MET is an MI-based approach that includes 2-4 behavioral treatment sessions based on the Platform Treatment Manual

Also known as: Behavioral therapy

IL-22 (F-652), Prednisone Placebo, Acamprosate, MI and MET; Prednisone, IL-22 (F-652) Placebo, Acamprosate, MI, and MET

Usual Care BEHAVIORAL

defined as a brief intervention with advice not to drink alcohol-containing beverages and referral to a 12-step program

IL-22 (F-652), Prednisone Placebo, and usual care; Prednisone, IL-22 (F-652) Placebo, and usual care

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Samer Gawrieh: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (6)

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Louisville

Louisville, Kentucky, 40292, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55902, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

University of Texas Southwestern Medical School

Dallas, Texas, 15260, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

RECRUITING

MeSH Terms

Interventions

Interleukin-22; eflepedocokin alfa; Prednisone; Acamprosate; Motivational Interviewing; Behavior Therapy

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Directive Counseling; Counseling; Mental Health Services; Behavioral Disciplines and Activities; Health Services; Health Care Facilities Workforce and Services; Psychotherapy

Central Study Contacts

Savannah Yarnelle

CONTACT

3172786424; samussel@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine. Director, Hepatology Clinical and Research Fellowship Program Clinical Director, NIAAA Alcoholic Hepatitis Network DCC

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: July 11, 2025
• Study Start: January 27, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (6)