Acute on Chronic Hepatitis (AOCH) MedDRA version: 13.1 Level: PT Classification code 10019755 Term: Hepatitis chronic active System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
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: Extrac
Sponsors
VITAL THERAPIES INCORPORATED
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
Exclusion criteria: Subjects must NOT meet any of the following exclusion criteria: 1) Platelets 3.5; OR 5) Septic shock as defined by a positive blood culture and two or more of the following: a. Systolic blood pressure 20 breaths per minute OR a PaCO2 12000 cells/mm3 ( 12 X 109 cells/L); OR 6) Evidence of major hemorrhage as indicated by: • requiring = 4 units packed red blood cells within a 48 hour period, OR • hemodynamic instability (sustained pulse >120 beats/min AND systolic blood pressure <100 mmHg over one hour). Subjects with a recent history of gastrointestinal hemorrhage who have been successfully treated and remain hemodynamically stable for a period of 48 hours before randomization will be eligible for the study if the investigator determines the subject to be at low risk for rebleeding; OR 7) Evidence (by physical exam, history, or laboratory evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, hepatitis due to herpes virus, Wilson’s disease, or Budd-Chiari syndrome; OR 8) Known history of hepatocellular carcinoma beyond the Milan criteria and/or occlusive portal vein thrombosis impairing hepatopedal flow; OR 9) Evidence of spontaneous bacterial peritonitis associated with an uncontrolled systemic infection; OR 10) Evidence of brain death as determined by blood flow studies positive for herniation AND/OR absence of pupillary reflex; OR 11) Systolic blood pressure < 85 mmHg OR MAP < 50 mmHg at Baseline; OR 12) Requirement for escalating doses of vasopressor support OR of an alpha-adrenergic agent for one hour or longer AND evidence of hemodynamic instability; OR 13) Subject at maximum vasopressor dose at Screen; OR 14) Clinical or radiographic evidence of a new stroke or intracerebral bleeding; OR 15) Seizures uncontrolled by medication; OR 16) Acute myocardial infarction based on clinical and/or electrocardiographic evidence; OR 17) Lung disease defined by a PaO2 <60 mm Hg on room air, acute respiratory distress syndrome (ARDS), or a history of severe COPD or interstitial lung disease; OR 18) Pregnancy as determined by ß-human chorionic gonadotropin (HCG) results, or lactation; OR 19) Participation in another investigational drug, biologic, or device study within one month of enrollment. Subjects who are enrolled in an observational study will be eligible for this trial; OR 20) Previous liver transplant; OR 21) Previous participation in a clinical trial involving ELAD®; OR 22) Have either a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or such local equivalent) in place.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ;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.;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. ;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 sc | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
United Kingdom, United States
Contacts
Public ContactCLINICAL TRIAL MANAGER
PREMIER RESEARCH GROUP LIMITED
Outcome results
None listed