Alcohol-Induced Liver Decompensation (AILD)
Conditions
Interventions
Product Name: Allogenic differentiated adult cloned immortalized human hepatoblastoma cells derived from a subclon
Product Code: ELAD SYSTEM
Pharmaceutical Form: Living tissue equivalent
INN or Propos
Sponsors
Vital Therapies, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet ALL inclusion criteria to be eligible for the study: 1. Age ?18; 2. Total bilirubin ?16 mg/dL (?273.6 µmol/L); 3. A clinical diagnosis of alcohol-induced liver decompensation (AILD), based upon lab test or medical history or family interview with a causal relationship and temporal association (6 weeks or less) of alcohol use and hospital admission for this episode of AILD; 4. Maddrey score ?32; 5. Subjects must have severe acute alcoholic hepatitis (sAAH) diagnosed with either: a. A confirmatory liver biopsy, OR b. Two or more of the following: i. Hepatomegaly, ii. AST > ALT, iii. Ascites, iv. Leukocytosis (WBC count above lab normal at site); 6. Subjects will be classified as either: a. AILD that is sAAH with no underlying liver disease other than alcoholic liver disease, OR b. AILD that is sAAH with evidence of underlying liver disease other than alcoholic liver disease which must be documented by: i. Liver biopsy, AND/OR ii. Laboratory findings, AND/OR iii. Medical history; 7. Not eligible for liver transplant during this hospitalization; 8. Subject or legally-authorized representative must provide Informed Consent; 9. Subject must be eligible for Standard of Care treatment as defined in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects must NOT have any of the following exclusion criteria: 1. Age ?50; 2. Platelet count 2.5; 4. Serum Creatinine ?1.3 mg/dL (?115.04 µmol/L); 5. MELD score ?30; 6. AST >500 IU/L; 7. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptoms, etc.) indicated by any of the following: a. Presence of sepsis or septic shock; OR b. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Randomization; OR c. Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization; OR d. Clinical and radiological signs of pneumonia; 8. Evidence of reduction in total bilirubin of 20% or more in the previous 72 hours. Bilirubin measurements must be taken at least 12 hours after any procedure known to artificially alter serum bilirubin (e.g., administration of packed red blood cells, plasma exchange); 9. Evidence of hemodynamic instability as defined by the following: a. Systolic blood pressure <90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR b. Mean arterial pressure (MAP) <60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR c. Requirement for escalating doses of vasopressor support prior to Screening; OR d. Subject on vasopressors, including but not limited to those listed below, at doses above the following at Screening or Randomization: ? Dobutamine: 5.0 µg/kg/min ? Dopamine: 2.0 µg/kg/min ? Norepinephrine: 0.02 µg/kg/min ? Phenylephrine: 1.0 µg/kg/min ? Vasopressin: 0.02 U/min 10. Evidence of active bleeding, major hemorrhage defined as requiring ?2 units packed red blood cells to maintain a stable hemoglobin occurring within 48 hours prior to Randomization, or with banding of gastroesophageal varices during the 7 days immediately preceding screening; 11. Clinical evidence of liver size reduction due to cirrhosis [liver size of the craniocaudal diameter (sagittal view) <10 cm when measured on the mid clavicular line (or equivalent measurement) by ultrasound, or liver volume <1200 cc as determined by CT or MRI], unless Investigator interpretation of the clinical evidence indicates liver size of <10 cm or volume <1200 cc is not considered reduced for the individual subject, and Sponsor agrees; 12. Occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction; 13. Evidence by physical exam, history, or laboratory evaluation, of significant concomitant disease with a life expectancy of less than 3 months, including, but not limited to: a. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease; b. Cancer that has metastasized or has not yet been treated; c. Severe metabolic abnormalities that have not been corrected (See Section 5.1.3); 14. Subject has chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome); 15. Subject ventilated or intubated; 16. Subject on hemodialysis; 17. Subject has liver disease related to homozygous hemachromotosis, Wilson?s disease, has non-alcoholic fatty liver disease, or Budd-Chiari Syndrome. 18. Serological evidence (including viral titers) of active viral hepatitis A, B or C infection. If the investigator suspects that the subject may be at risk for viral he
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate safety and efficacy of ELAD® with respect to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) through at least Study Day 91, with follow-up Protocol VTL-308E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTL-308 study termination (after the last surviving enrolled subject completes Study Day 91). The primary objective will be assessed using a Kaplan-Meier survival analysis of the modified Intent-to-Treat (mITT) population utilizing a log-rank test.;Secondary Objective: The secondary objective is to evaluate the proportion of survivors at Study Day 91 using a chi-squared test.;Primary end point(s): Overall survival (OS) will be assessed using a Kaplan-Meier survival analysis of the modified intent-to-treat (mITT) population utilizing a log-rank test, with follow-up Protocol VTL-308E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTL-308 study termination. Model-based estimates and confidence limits will be calculated for median survival by treatment group and the hazard ratio and its confidence limits. This analysis will also be carried out on the ITT, Per-Protocol (PP) and Safety populations as sensitivity analyses. Two-tailed alpha for the log-rank test will be set at 0.05. The statistical analysis plan will outline the methods used to account for missing data in this and all other analyses. The statistical analysis plan will also evaluate differences in standard of care between the groups that may affect subject outcome, such as differences in the administration of steroid therapy, and define analytical strategies to deal with those differences should they arise.;Timepoint(s) of evaluation of this end point: After all enrolled subjects either complete Study Day 91, are lost to follow up or withdraw consent, or die bef | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A chi-square test will be used to evaluate the proportion of subjects who survived at End of Study Day 91 based on the mITT population. Two-tailed alpha will be set at 0.05. This analysis will also be carried out on the ITT, PP and Safety populations as sensitivity analyses.;Timepoint(s) of evaluation of this end point: End of Study Day 91. | — |
Countries
Austria, Germany, Ireland, Spain, United Kingdom, United States
Contacts
Public ContactVP, Regulatory Affairs and QA
Vital Therapies, Inc.
Outcome results
None listed