EFFICACY AND SAFETY OF ELAD IN SUBJECTS WITH ACUTE ON CHRONIC HEPATITIS (AOCH)

INTERVENTION: Product Name: ELAD Product Code: ELAD SYSTEM Pharmaceutical Form: Living tissue equivalent INN or Proposed INN: Human C3A hepatoblastoma cells Current Sponsor code: ELAD Other descriptive name: Extracorporeal Liver Assist system Concentration unit: Other Concentration type: equal Concentration number: 4‐ CONDITION: Acute on Chronic Hepatitis (AOCH) ; MedDRA version: 13.1 Level: PT Classification code 10019755 Term: Hepatitis chronic active System Organ Class: 10019805 ‐ Hepatobiliary disorders Therapeutic area: Body processes [G] ‐ Metabolic Phenomena [G03] SECONDARY OUTCOME: Secondary end point(s): Safety will be evaluated through monitoring of adverse events (AEs), physical examinations, vital signs, and laboratory test results. Timepoint(s) of evaluation of this end point: Continuously through out treatment period and posat treatment study days 14, 21, 63 and 91 INCLUSION CRITERIA: Subjects must meet ALL inclusion criteria to be eligible for the study at baseline: 1) Age =18 =67 years; AND 2) Acute decompensation of chronic liver disease over the preceding 28 days; AND 3) MELD score between 18 and 35, inclusive; AND 4) Diagnosis of AOCH (AAH or non‐AAH); AND 5) Subject or designated representative must provide Informed Consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5 PRIMARY OUTCOME: Main Objective: The objective of this study is to evaluate the efficacy and safety of ELAD to stabilize liver function during the acute phase of AOCH. Stabilization is measured using the time to progression (TTP) with progression defined as the earlier of death or an increase of 5 points or more in MELD score at defined times post‐baseline. Differences between treatment groups in time to progression will be analyzed based on the time of the death or the first observed increase of at least 5 points from Baseline MELD score at least 24 hours following the end of the Treatment Period, then at least on Study Days 7, 14, 21, 28, 63 and 91.; Primary end point(s): The primary study objective is to establish that treatment with the ELAD system results in stabilized liver function for patients during the acute phase of AOCH. Secondary Objective: Secondary efficacy analyses will evaluate the proportion of Progression Free Survivors using a chi‐square test to compare the proportion of subjects who survived without MELD‐based progression (as defined in the Primary Endpoint) at Study Day 28 (27 days following Baseline) and Study Day 91 (90 days following Baseline). Two‐tailed alpha will be set at 0.05. In addition these secondary efficacy analyses will be performed using a Cochran‐Mantel‐Haenszel test stratified by subject classification (AAH or non‐AAH) to compare the proportion of subjects who have survived without MELD‐based progression (as defined in the Primary Endpoint) at Study Day 28 and Study Day 91 (27 and 90 days following Baseline respectively). Two‐tailed alpha will be set at 0.05.; ; Safety will be evaluated through monitoring of adverse events (AEs), physical examinations, vital signs, and laboratory test results. Timepoint(s) of evaluation of this end point: A Kaplan‐Meier analysis will be used to evaluate differences between treatment groups in time to progression (TTP) based on death or the first observed increase of at least 5 points from Baseline MELD score at least 24 hours after the ELAD Treatment Period is ended and up to Study Day 91 (90 days following Baseline). This analysis will be stratified based on the classification of a subject as either AAH or non‐AAH diagnosis. A stratified log‐rank test will be used to compare the Kaplan‐Meier curves with 2‐tail alpha set at 0.05.