Acute Alcoholic Hepatitis
Conditions
Brief summary
The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) through at least Study Day 91. The secondary objective is to evaluate the proportion of survivors at Study Day 91 using a chi-squared test.
Detailed description
The ITT population includes all randomized subjects assigned to the group to which they were randomized, irrespective of actual treatment administered. Participant, Baseline Characteristics, and Outcome Measures used the ITT population. The safety population is defined as all subjects who are randomized based on actual treatment received. All serious adverse events and all non-serious adverse events analyses used the safety population.
Interventions
BIOLOGICALELAD System
An extracorporeal human hepatic cell-based liver treatment
Standard medical treatment as defined by the protocol
Sponsors
Vital Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
No
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 AILD that is 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); Note: Subjects will be classified as either: 1. AILD that is sAAH with no underlying liver disease other than alcoholic liver disease, OR 2. 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; 6. Not eligible for liver transplant during this hospitalization; 7. Subject or legally-authorized representative must provide Informed Consent; 8. Subject must be eligible for Standard of Care treatment as defined in the protocol.
Exclusion criteria
Subjects must NOT have any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to at least Study Day 91, with protocol VTL-308E providing additional survival data (at 6, 9, 12, 24 months) at the time of database lock (28 August 2018). | The primary endpoint of the study was a comparison of overall survival (OS) between the ELAD-treated and Control groups, with protocol VTL-308E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (28 Aug 2018). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Survivors at Study Day 91 | Up to Study Day 91 | Assess the proportion of survivors at Study Day 91 |
| Number of Subjects With Early Change in Bilirubin Levels at Study Day 7 | Up to Study Day 7 | To estimate the effect of ELAD on the number of subjects achieving a 20% reduction in total bilirubin by Day 7 (ECBL20 Yes) |
Countries
Austria, Germany, Ireland, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ELAD System This group will receive treatment with ELAD plus standard of care therapy.
ELAD System: An extracorporeal human hepatic cell-based liver treatment | 78 |
| Standard of Care (Control) This group will receive standard of care therapy as defined in the protocol.
Standard of Care (Control): Standard medical treatment as defined by the protocol | 73 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| VTL-308 | Death | 14 | 16 |
| VTL-308 | Withdrawal by Subject | 0 | 1 |
| VTL-308E | Death | 9 | 7 |
| VTL-308E | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | ELAD System | Standard of Care (Control) | Total |
|---|---|---|---|
| Age, Customized Age Between 18 and 35 years | 23 Participants | 22 Participants | 45 Participants |
| Age, Customized Age Between 36 and 50 years | 55 Participants | 51 Participants | 106 Participants |
| Baseline MELD Score | 24.8 MELD Score STANDARD_DEVIATION 2.37 | 25.6 MELD Score STANDARD_DEVIATION 2.35 | 25.2 MELD Score STANDARD_DEVIATION 2.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 70 Participants | 67 Participants | 137 Participants |
| Region of Enrollment Austria | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Germany | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Ireland | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Spain | 5 participants | 3 participants | 8 participants |
| Region of Enrollment United Kingdom | 11 participants | 11 participants | 22 participants |
| Region of Enrollment United States | 57 participants | 52 participants | 109 participants |
| Sex: Female, Male Female | 31 Participants | 29 Participants | 60 Participants |
| Sex: Female, Male Male | 47 Participants | 44 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 76 | 17 / 75 |
| other Total, other adverse events | 76 / 76 | 74 / 75 |
| serious Total, serious adverse events | 47 / 76 | 42 / 75 |
Outcome results
Primary
Overall Survival
The primary endpoint of the study was a comparison of overall survival (OS) between the ELAD-treated and Control groups, with protocol VTL-308E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (28 Aug 2018).
Time frame: Up to at least Study Day 91, with protocol VTL-308E providing additional survival data (at 6, 9, 12, 24 months) at the time of database lock (28 August 2018).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELAD System | Overall Survival | 55 Participants |
| Standard of Care (Control) | Overall Survival | 51 Participants |
Comparison: The primary endpoint was assessed using a Kaplan-Meier survival analysis of the Intent-to-treat (ITT) population utilizing a log-rank test.p-value: 0.76295% CI: [0.509, 1.64]Log Rank
Secondary
Number of Subjects With Early Change in Bilirubin Levels at Study Day 7
To estimate the effect of ELAD on the number of subjects achieving a 20% reduction in total bilirubin by Day 7 (ECBL20 Yes)
Time frame: Up to Study Day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELAD System | Number of Subjects With Early Change in Bilirubin Levels at Study Day 7 | 38 Participants |
| Standard of Care (Control) | Number of Subjects With Early Change in Bilirubin Levels at Study Day 7 | 24 Participants |
p-value: 0.048Chi-squared
Secondary
Number of Survivors at Study Day 91
Assess the proportion of survivors at Study Day 91
Time frame: Up to Study Day 91
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELAD System | Number of Survivors at Study Day 91 | 63 Participants |
| Standard of Care (Control) | Number of Survivors at Study Day 91 | 57 Participants |
p-value: 0.6829Chi-squared