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Larsucosterol for people with severe alcohol-associated hepatitis

RE-AHFIRM (RandomizEd Study of Larsucosterol in Alcohol-associated Hepatitis to Confirm saFety and effIcacy of tReatMent)

Phase 3 Interventional Bausch Health Americas, Inc. · NCT07428538

This trial will test whether larsucosterol helps people with severe alcohol-associated hepatitis survive 90 days without needing a liver transplant.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment350 (estimated)
Ages18 Years and up
SexAll
SponsorBausch Health Americas, Inc. Industry-sponsored
Locations48 sites (Birmingham, Alabama and 47 other locations)
Trial IDNCT07428538 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized interventional trial compares larsucosterol to placebo in adults hospitalized with severe alcohol-associated hepatitis. The primary outcome is transplant-free survival through Day 90, and participants are randomized to receive larsucosterol or placebo and followed for safety and clinical outcomes. Eligible patients have severe AH defined by pre-treatment Maddrey Discriminant Function ≥32 and MELD scores of 21–30, with recent heavy alcohol use and elevated bilirubin. The study is conducted at multiple U.S. hospital centers and collects clinical labs and event data over the 90-day follow-up period.

Who should consider this trial

Good fit: Ideal candidates are hospitalized adults with severe alcohol-associated hepatitis (Maddrey DF ≥32 and MELD 21–30), recent heavy alcohol use, and bilirubin >3 mg/dL who can provide informed consent or have a legally acceptable representative.

Not a fit: Patients with milder disease, MELD scores outside the 21–30 range, non-alcohol causes of liver injury, or those who do not meet the alcohol-use or lab criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, larsucosterol could reduce short-term mortality and lower the need for liver transplantation in people with severe alcohol-associated hepatitis.

How similar studies have performed: Earlier-phase studies and preclinical data suggested potential benefit for larsucosterol, but large-scale Phase 3 evidence is still limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 47 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions HepatitisAlcoholic hepatitisalcohol-associated liver diseaseLiver transplantAlcohol-associated hepatitis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.