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NCT07428538PHASE3Recruiting

Study to Evaluate the Safety and Efficacy of Larsucosterol in Participants With Alcohol-associated Hepatitis (AH)

Bausch Health Americas, Inc.

Start Date

1/29/2026

Completion Date

2/1/2028

Summary

The primary purpose of this study is to evaluate the safety and efficacy of larsucosterol, as determined by transplant-free survival through Day 90 in participants with severe alcohol-associated hepatitis (AH) with pre-treatment Maddrey Discriminant Function (MDF) score greater than or equal to (\>=) 32 and Model for End-stage Liver Disease (MELD) scores 21-30, inclusive.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria- A participant will be eligible for inclusion in this study if he/she meets all the following criteria: 1. Able to provide written informed consent (either from participant or participant's legally acceptable representative). 2. Onset of jaundice within 8 weeks before hospital admission. 3. Average daily consumption of greater than (\>) 40 (females) or \>60 (males) grams alcohol for 6 months or longer, with less than (\<) 8 weeks of abstinence before the onset of jaundice. Judgment regarding daily and long-term alcohol use and onset of jaundice will be made and documented by the site Investigator. 4. The determination of AH will be based on typical serum chemistry (as determined by local laboratory): 1. Serum total bilirubin \>3.0 milligrams per deciliter (mg/dL) (required at randomization) 2. ALT \<400 international unit per Liter (IU/L) (required at randomization) 3. 50 \<AST \<400 IU/L 4. AST \<400 IU/L (required at randomization) 5. AST \>50 IU/L (at any time since current hospital admission or leading to this current hospitalization) 6. AST/ALT \>1.5 (at any time since current hospital admission or leading to this current hospitalization) 5. Maddrey discriminant function (MDF) \>=32, assuming a control prothrombin time of 12 seconds. NOTE: If a local laboratory's control time differs from 12 seconds, then the local laboratory's control time should be used. If control time is not stated or is stated as a range, the control time should be calculated by the formula prothrombin time/INR. 6. Original Model for End-stage Liver Disease (MELD; not MELD-Na) score: 21-30 (inclusive). 7. Male or female participants 18 years of age or older. 8. Women of child-bearing potential (defined as females who are not surgically sterile or who are not over the age of 52 and amenorrheic for at least 12 months) must utilize appropriate birth control throughout the 90-day portion of the study. Acceptable methods that may be used are abstinence, birth control pills ("The Pill") or patch, diaphragm, IUD (coil), vaginal ring, condom, surgical sterilization or progestin implant or injection, or sexual activity limited to a sterile (e.g., vasectomized) male partner. 9. Male participants must agree to use a medically acceptable method of contraception/birth control and refrain from sperm donation throughout the 90-day portion of the study. 10. Participants must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists. 11. Participants must be dosed within 9 calendar days (216 hours) of hospital admission inclusive of time spent in other hospital(s) Exclusion Criteria- A participant will be excluded from the study if he or she meets any of the following criteria: 1. Participants using systemic corticosteroids for current AH before enrollment or having a history of using systemic corticosteroids for more than 8 days in the last 30 days prior to screening. NOTE: Inhaled, topical, or local corticosteroid injections are permitted NOTE: A participant who has a confirmed diagnosis of hypoadrenalism and is taking a physiological replacement dose of hydrocortisone (or equivalent) is permitted to take part in the trial 2. Participants experiencing or considered at high risk for alcohol withdrawal seizures or delirium tremens. 3. Active infection (such as spontaneous bacterial peritonitis \[SBP\], urinary tract infection \[UTI\], cellulitis, pneumonia, bacteremia, acute viral hepatitis, uncontrolled HIV, and active SARS CoV2 infection). 1. Participants who are febrile with leukocytosis are also excluded until active infection has been excluded to the satisfaction of the PI in consultation with the medical monitor. 2. Participants with bacterial infections may be enrolled provided they remain in the enrollment window and the infection is adequately treated. For example, participants with bacterial peritonitis may be considered for enrollment once the infection has been treated and follow up paracentesis confirms the absence of SBP. 3. Participants with systemic fungal infection of any kind cannot be considered for this trial. 4. Serum creatinine \>2.5 mg/dL. 5. Participants undergoing continuous veno-venous hemodialysis (CVVH). 6. Gastrointestinal bleeding not controlled by local therapy (i.e., band ligation or injection sclerotherapy). Participant who are at high risk of rebleeding or likely in need of TIPS insertion should be excluded. 7. TIPS insertion or variceal embolization within the last 4 weeks. 8. Known portal vein occlusion. 9. A history of pre-admission refractory ascites defined as more than 4 paracenteses in the previous 8 weeks despite diuretic therapy. 10. Liver biopsy (if carried out) with findings not compatible with AH. NOTE: A post-dose liver biopsy that is not compatible with AH will not be considered a protocol deviation. 11. Stage \>=3 hepatic encephalopathy by West Haven criteria. 12. Participants with medical conditions that are expected to pose a high risk of short-term (less than or equal to \[\<=\] 90 days) mortality unrelated to alcohol-associated hepatitis, or that may confound assessment of 90-day survival in the Investigator's judgement. Examples include, but are not limited to: 1. Severe concomitant cardiopulmonary disease (e.g., New York Heart Association \[NYHA\] Class III or IV heart failure) 2. Clinically significant cardiac arrhythmia (e.g., sustained ventricular tachycardia, unmanaged atrial fibrillation, QTc \>=500 msec, or high-grade AV block) 3. Ventilator-dependent respiratory failure, or Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Stage III or IV chronic obstructive pulmonary disease \[COPD\]) 4. End-stage renal disease requiring chronic, ongoing dialysis 5. Severe uncontrolled endocrine or metabolic disorders 6. Severe psychiatric illness likely to interfere with study participation 7. Hypotension/shock as defined by the North American Consortium for the study of End-stage Liver Disease (NACSELD) criteria (i.e., Mean Arterial Pressure \[MAP\] \<60 millimeter of mercury (mmHg), despite adequate fluid resuscitation and cardiac output) 13. Other concomitant cause(s) of liver disease as a result of: 1. Autoimmune liver disease 2. Ischemic hepatitis 3. Wilson disease or alpha 1 antitrypsin deficiency 4. Vascular liver disease (e.g., Budd-Chiari) 5. Drug induced liver disease 6. Surface antigen positive hepatitis B (HBsAg+). NOTE: Participants with isolated core antibody (anti-HBc) or who are on stable antiviral medication with known viral suppression are not excluded, but appropriate HBV prophylaxis should be considered if steroid dosing \>4 weeks is anticipated. 7. Acute hepatitis A (if test performed per SOC) 8. Acute HCV or chronic hepatitis C with a history of decompensated cirrhosis. NOTE: participants with stable chronic HCV or successfully treated HCV are not excluded 9. Acute hepatitis E (if test performed per SOC) 10. Acute cytomegalovirus (CMV) viral hepatitis (if test performed per SOC) 14. Any known active malignancy or any malignancy diagnosed within the last five years other than curable skin cancer (basal cell or squamous cell carcinomas). 15. Existing or intended pregnancy or breast feeding. 16. Participation in another interventional clinical trial within 30 days of Screening. 17. History of organ transplantation other than corneal transplant. 18. Underlying disease that, in the opinion of the site Investigator, might be complicated or exacerbated by proposed treatments or might confound assessment of study drug. 19. Participant listed for liver transplant (LT) prior to study drug administration. 20. Concern of participant's willingness and ability to be compliant with the schedule of protocol assessments, per the Investigator's judgement.

Interventions

DRUG

Larsucosterol

DRUG

Placebo

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Conditions

Hepatitis

Locations

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama 35294

United States

University of South Alabama

Mobile, Alabama 36602

United States

Banner - University Medical Center, Phoenix, Arizona

Phoenix, Arizona 85006

United States

Mayo Clinic - Phoenix

Phoenix, Arizona 85054

United States

Southern California GI & Liver Centers - Coronado

Coronado, California 92118

United States

Scripps

La Jolla, California 92037

United States

Cedars Sinai Medical Center

Los Angeles, California 90048

United States

UCLA Health - Ronald Reagan Medical Center

Los Angeles, California 90095

United States

Stanford Medicine - Clinical and Translational Research Unit - Redwood City

Redwood City, California 94063

United States

University of California at Davis Medical Center

Sacramento, California 95757

United States

Sutter Health

San Francisco, California 94109

United States

Yale School of Medicine

New Haven, Connecticut 06510

United States

Georgetown University Medical Center

Washington D.C., District of Columbia 20007

United States

Mayo Clinic

Jacksonville, Florida 32202

United States

Reliant Medical Research

Miami, Florida 33131

United States

University of Miami

Miami, Florida 33131

United States

AdventHealth Transplant Institute

Orlando, Florida 32804

United States

AdventHealth Medical Campus

Tampa, Florida 33602

United States

Tampa General Hospital

Tampa, Florida 33606

United States

Piedmont Atlanta Hospital - Piedmont Transplant Institute

Atlanta, Georgia 30309

United States

Augusta University

Augusta, Georgia 30901

United States

Northwestern University - Feinberg School of Medicine

Chicago, Illinois 60601

United States

Rush University Medical Center

Chicago, Illinois 60612

United States

Loyola University Medical Center (LUMC)

Maywood, Illinois 60153

United States

Indiana Institute for Medical Research (Indiana VA)

Indianapolis, Indiana 46204

United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa 52242

United States

University of Kentucky -Chandler Medical Center

Lexington, Kentucky 40507

United States

Robley Rex VA Medical Center

Louisville, Kentucky 40206

United States

Tulane University Health Sciences Center - Tulane Avenue

New Orleans, Louisiana 70112

United States

Maine Medical Center - Bramhall Campus

Portland, Maine 04102-3134

United States

Mercy Medical Center - The Institute for Digestive Health and Liver Disease

Baltimore, Maryland 21202

United States

Johns Hopkins Hospital

Baltimore, Maryland 21287

United States

Tufts Medical Center

Boston, Massachusetts 02108

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Boston University School of Medicine

Boston, Massachusetts 02118

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

UMass Chan Medical School

Worcester, Massachusetts 01655

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Henry Ford Hospital System

Detroit, Michigan 48202

United States

University of Minnesota Medical Center

Minneapolis, Minnesota 55414-2924

United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri 64106

United States

University of Nevada Las Vegas

Las Vegas, Nevada 89101

United States

Virtua Medical Group (VMG) - Virtua Center for Liver Disease - Toms River

Camden, New Jersey 08102

United States

Rutgers University New Jersey Medical School

Newark, New Jersey 07103-2425

United States

University of New Mexico (UNM) Hospital

Albuquerque, New Mexico 87106-4713

United States

Northwell Health Physician Partners Sandra Atlas Bass Center for Liver Diseases

Manhasset, New York 11030

United States

Columbia University Medical Center (CUMC) - Presbyterian Hospital and Vanderbilt Clinic

New York, New York 10007

United States

NYU Langone Health

New York, New York 10016

United States

University of Rochester Medical Center

Rochester, New York 14604

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Levine Cancer Institute / Atrium Health

Charlotte, North Carolina 28204

United States

Duke University Hospital

Durham, North Carolina 27710

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Cleveland Clinic

Cleveland, Ohio 44114

United States

The Ohio State University Wexner Medical Center (OSUWMC)

Columbus, Ohio 43210

United States

Oregon Health & Science University

Portland, Oregon 97204

United States

Penn State Health, Milton S. Hershey Medical Center

Hershey, Pennsylvania 17033

United States

VA Medical Center - Philadelphia

Philadelphia, Pennsylvania 19104-4551

United States

University of Pennsylvania Hospital

Philadelphia, Pennsylvania 19104

United States

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania 19107

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Temple University Hospital

Philadelphia, Pennsylvania 19140

United States

University of Pittsburgh

Pittsburgh, Pennsylvania 15222

United States

Ralph H. Johnson Department of Veterans Affairs Medical Center

Charleston, South Carolina 29401

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Galen Medical Group - Galen Hepatology

Chattanooga, Tennessee 37402

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37219

United States

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas 75203

United States

Baylor Scott White Research Institute - Dallas

Dallas, Texas 75246

United States

North Texas Gastroenterology

Denton, Texas 76201

United States

Baylor Scott & White All Saints Medical Center - Forth Worth

Fort Worth, Texas 76104

United States

Clinical Trial Network - Houston

Houston, Texas 77002

United States

Baylor College of Medicine (BCM) - Baylor Clinic

Houston, Texas 77030

United States

Methodist Healthcare - Methodist Hospital Specialty and Transplant

San Antonio, Texas 78205

United States

Baylor Scott White Research Institute - Temple

Temple, Texas 76501

United States

Intermountain Transplant Clinic

Murray, Utah 84107

United States

University of Utah Health - University of Utah

Salt Lake City, Utah 84132

United States

University of Virginia Health

Charlottesville, Virginia 22908

United States

Bon Secours Liver Institute of Richmond

Richmond, Virginia 23226

United States

Richmond VA Medical Center

Richmond, Virginia 23249

United States

Swedish Medical Center

Seattle, Washington 98101

United States

UW Medicine-Harborview Medical Center

Seattle, Washington 98101

United States

Marshall Health

Huntington, West Virginia 25701

United States

University of Wisconsin-Madison

Madison, Wisconsin 53703

United States