Alcoholic hepatitis MedDRA version: 20.0 Level: LLT Classification code 10001624 Term: Alcoholic hepatitis System Organ Class: 100000004871
Conditions
Interventions
Product Name: DUR-928 30mg
Product Code: DUR-928
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DUR-928
CAS Number: 1174047-40-5
Current Sponsor code: DUR-928
Other de
Sponsors
DURECT Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent (either from subject or subject’s legally acceptable representative) 2. Onset of jaundice within prior 8 weeks 3. Average daily consumption of > 40 (females) or > 60 (males) grams alcohol for 6 months or longer, with 3.0 mg/dL • 50 1.5 NOTE: Labs values on the day of randomization must include serum total bilirubin > 3.0 mg/dL and AST and ALT =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Subjects taking systemic corticosteroids for a duration exceeding 8 days in the 30 days prior to screening. NOTE: Inhaled, topical, or local corticosteroid injections are permitted 2. Subjects 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], bacteremia, acute viral hepatitis, uncontrolled HIV, and active SARS CoV2 infection). a. Subjects 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. b. Patients with bacterial peritonitis may be considered for enrollment once the infection has been treated and follow up paracentesis confirms the absence of SBP. c. Patients with fungal infection of any kind cannot be considered for this trial. 4. Serum creatinine >2.5 mg/dL 5. Criterion removed as part of Protocol Amendment 2, but placeholder kept to maintain consistency in subsequent criteria numbering 6. Subjects undergoing continuous veno-venous hemodialysis (CVVH) 7. Uncontrolled gastrointestinal bleeding 8. A history of pre-admission refractory ascites defined as more than 4 paracenteses in the previous 8 weeks despite diuretic therapy. 9. Liver biopsy (if carried out) with findings not compatible with AH 10. Stage = 3 hepatic encephalopathy by West Haven criteria 11. Any severe concomitant cardiovascular, renal, endocrine, pulmonary (including ventilator dependent or COPD Global Obstructive Lung Disease [GOLD] stage III or IV), psychiatric disorder, or multi-organ failure 12. Other concomitant cause(s) of liver disease as a result of: a. Autoimmune liver disease b. Ischemic hepatitis c. Wilson disease or alpha 1 antitrypsin deficiency d. Vascular liver disease (e.g., Budd-Chiari) e. Drug induced liver disease f. Surface antigen positive hepatitis B (HBsAg+). NOTE: subjects with isolated core antibody (anti-HBc) or who are on stable antiviral medication with known viral suppression are not excluded g. Acute hepatitis A (if test performed per SOC) h. Acute HCV or chronic hepatitis C with a history of decompensated cirrhosis. NOTE: subjects with stable chronic HCV or successfully treated HCV are not excluded i. Acute hepatitis E (if test performed per SOC) j. Acute cytomegalovirus (CMV) viral hepatitis (if test performed per SOC) k. Acute Epstein-Barr virus (EBV) viral hepatitis (if test performed per SOC) NOTE: A spurious finding, such as the incidental finding of moderately elevated antinuclear antibody (ANA) or anti-smooth muscle antibody (ASMA) titer is not, by itself, a mandatory exclusion criterion unless accompanied by other evidence suggestive of a probable disease other than AH. 13. Any active malignancy or any malignancy diagnosed within the last five years other than curable skin cancer (basal cell or squamous cell carcinomas) 14. Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications 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 a corneal transplant 18. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and efficacy, 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;Secondary Objective: Evaluate the efficacy, 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;Primary end point(s): Difference in 90-day mortality or transplant between IV DUR-928, 30 mg or 90 mg, and placebo;Timepoint(s) of evaluation of this end point: 90-day | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo 2. Difference in 28-day mortality or transplant between IV DUR-928, 30 mg or 90 mg, and placebo 3. Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo;Timepoint(s) of evaluation of this end point: 28-day and 90 days | — |
Countries
Australia, Austria, Belgium, France, Germany, United Kingdom, United States
Contacts
Public ContactClinical Operations
DURECT Corporation
Outcome results
None listed