A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment

Overview

About this study

The purpose of this study is to evaluate the safety and effectiveness, as determined by 90-day incidence of mortality or transplant, for intravenous (IV) DUR-928 (30 mg or 90 mg) in subjects with severe alcohol-associated hepatitis, also known as severe alcoholic hepatitis, (AH) with pre-treatment Maddrey Discriminant Function (MDF) score ≥ 32 and MELD scores 21-30. Additionally, to evaluate the effectiveness, as determined by 90-day mortality and 28-day mortality with or without transplant for IV DUR-928 (30 mg or 90 mg) in subjects with severe AH.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Able to provide written informed consent (either from subject or subject's legally acceptable representative).
  • Onset of jaundice within prior 8 weeks.
  • Average daily consumption of > 40 (females) or > 60 (males) grams of alcohol for 6 months or longer, with < 8 weeks of abstinence before the onset of jaundice. Judgment
  • regarding daily and long-term alcohol use and onset of jaundice will be made by the site investigator.
  • Serum chemistry (as determined by local laboratory):
    • Serum total bilirubin > 3.0 mg/dL;
    • 50 < AST < 400 IU/L;
    • ALT < 400 IU/L;
    • AST/ALT > 1.5.
  • Maddrey's discriminant function ≥ 32 assuming a control prothrombin time of 12 seconds.
  • Model for End-stage Liver Disease (MELD) score: 21-30.
  • When the diagnosis of AH remains in question, a liver biopsy (if clinically feasible and that subject has no contra-indications) will be required. Historical biopsy is allowed.
  • Subjects must agree to use effective methods to prevent pregnancy while participating in the study.
  • Subjects must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists

Exclusion Criteria:

  • Subjects taking corticosteroids for a duration exceeding 7 days in the 30 days prior to screening.
  • Subjects experiencing alcohol withdrawal symptoms or treatment with Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol.
  • Active infection. Subjects who are febrile with leukocytosis are also excluded, even if there is no localizing diagnosis of infection.
  • Serum creatinine > 2.5 mg/dL or eGFR < 60 mL/min/1.73 m^2.
  • Subjects with acute kidney injury (AKl) or Hepatorenal syndrome.
  • Subjects undergoing continuous veno-venous hemodialysis (CVVH).
  • Uncontrolled active gastrointestinal bleeding.
  • Refractory ascites.
  • Liver biopsy (if carried out) with findings not compatible with AH.
  • Stage ≥ 3 hepatic encephalopathy by West Haven criteria.
  • Any severe concomitant cardiovascular, renal, endocrine, pulmonary, psychiatric disorder, or multi-organ failure.
  • Other concomitant cause(s) of liver disease.
  • Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) or any other malignancy diagnosed within the last five years.
  • Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications.
  • Existing or intended pregnancy or breast feeding.
  • Participation in another interventional clinical trial within 30 days of Screening.
  • History of organ transplantation, other than a corneal transplant.
  • Underlying diseases that, in the opinion of the site investigator, might be complicated or exacerbated by proposed treatments or might confound assessment of study drug.

Eligibility last updated 10/10/22/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Hugo Vargas, M.D.

Open for enrollment

Contact information:

Haydee Salgado Broncano R.N.

(480) 301-6198

SalgadoBroncano.Haydee@mayo.edu

More information

Publications

Publications are currently not available