Acute Alcoholic HepatitisPhase 3NCT02612428
Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects w/ AILD
A Phase 3 study testing ELAD System in people with Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 44 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Acute Alcoholic Hepatitis
- What is being tested?
- ELAD System
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 44 sitesin 6 countries
- Study dates
- Jan 2016to Sep 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects must meet ALL inclusion criteria to be eligible for the study:
- Age ≥18;
- Total bilirubin ≥16 mg/dL (≥273.6 µmol/L);
- 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;
- Maddrey score ≥32;
- Subjects must have AILD that is severe acute alcoholic hepatitis (sAAH) diagnosed with either:
Show all 14Show fewer
- 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:
- AILD that is sAAH with no underlying liver disease other than alcoholic liver disease, OR
- AILD that is sAAH with evidence of underlying liver disease other than alcoholic liver disease which must be documented by:
- Liver biopsy, AND/OR ii. Laboratory findings, AND/OR iii. Medical history;
- Not eligible for liver transplant during this hospitalization;
- Subject or legally-authorized representative must provide Informed Consent;
- Subject must be eligible for Standard of Care treatment as defined in the protocol.
Who cannot join
- Subjects must NOT have any of the exclusion criteria to be eligible for the study:
- Age ≥50;
- Platelet count <40,000/mm3;
- International Normalization Ratio (INR) >2.5;
- Serum Creatinine ≥1.3 mg/dL (≥115.04 µmol/L);
- MELD score ≥30;
Show all 42Show fewer
- AST >500 IU/L;
- 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:
- Presence of sepsis or septic shock; OR
- Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Randomization; OR
- Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization; OR
- Clinical and radiological signs of pneumonia;
- 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);
- Evidence of hemodynamic instability as defined by the following:
- Systolic blood pressure <90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
- Mean arterial pressure (MAP) <60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
- Requirement for escalating doses of vasopressor support prior to Screening; OR
- 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
- 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;
- 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;
- Occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;
- 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:
- Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
- Cancer that has metastasized or has not yet been treated;
- Severe metabolic abnormalities that have not been corrected (See Section 5.1.3);
- Subject has chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
- Subject ventilated or intubated;
- Subject on hemodialysis;
- Subject has liver disease related to homozygous hemachromotosis, Wilson's disease, has non-alcoholic fatty liver disease, or Budd-Chiari Syndrome;
- 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 hepatitis A, B or C, and no serology is available, then serologies must be obtained prior to Randomization, as a positive serology would be exclusionary;
- Pregnancy as determined by serum β-human chorionic gonadotropin (HCG) results, or subjects of child-bearing potential not willing to use effective means of contraception, without history of medical or surgical sterilization;
- Participation in another investigational drug, biologic, or device study within one month of enrollment, except for observational studies (the observational study setting should not affect the safety and/or efficacy of the VTL-308 clinical trial);
- Previous liver transplant;
- Previous enrollment in the treatment phase of another ELAD trial;
- Have a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or such local equivalent) or any other Advanced Directive limiting Standard of Care in place (the DNR/DNI criterion is not applicable in Europe);
- Refusal to participate in the VTL-308E follow-up study;
- Inability to provide an address for home visits.
Trial locations and contacts
44 sites in 6 countries.
44 sites in 6 countries
United States21 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Emory University Hospital
Atlanta, Georgia, 30322
Mercy Medical Center
Baltimore, Maryland, 21202
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Virginia Health System
Charlottesville, Virginia, 22908
Rush University Medical Center
Chicago, Illinois, 60612
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Missouri Hospital
Columbia, Missouri, 65212
Sharp Coronado Hospital
Coronado, California, 92118
The Pennsylvania State University and The Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Houston Methodist Hospital
Houston, Texas, 77030
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, 33136
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
University of Minnesota
Minneapolis, Minnesota, 55455
Rutgers University Hospital
Newark, New Jersey, 07101
Stanford University Medical Center
Palo Alto, California, 94304
Drexel University
Philadelphia, Pennsylvania, 19102
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
Montefiore Medical Center
The Bronx, New York, 10467
United Kingdom9 sites
Belfast Health and Social Care Trust
Belfast, BT9 7AB
Queen Elizabeth Hospital
Birmingham, B15 2GW
Doncaster Royal Infirmary
Doncaster, DN2 5LT
Ninewells Hospital and Medical School
Dundee, Scotland, DD1 9SY
Glasgow Royal Infirmary
Glasgow, Scotland, G40SF
Aintree University Hospital
Liverpool, England, L97AL
Royal London Hospital
London, E1 1BB
Royal Free Hospital
London, NW3 2QG
Nottingham University Hospital
Nottingham, NG7 2UH
Spain6 sites
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario Gregorio Marañón
Madrid, 28007
Hospital Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Universitario y Politécnico La Fe
Valencia, 46026
Hospital Clínico Universitario Lozano Blesa
Zaragoza, 50009
Germany5 sites
Medizinische Hochschule Hannover
Hanover, D-30625
Klinikum Landshut gemeinnuetzige GmbH
Landshut, Bavaria, 84034
Universitätsmedizin Mainz
Mainz, 55131
Universitätsklinikum Münster
Münster, D-48149
Universitätsmedizin Rostock
Rostock, D-18065
Austria2 sites
Medizinische Universität Graz
Graz, Styria, 8036
Medizinische Universität Klinik Für Innere Medizin III
Vienna, 1090
About this study
Official title: A Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)
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.
Read the 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.
- Conditions
- Acute Alcoholic Hepatitis
- Being tested
- ELAD System, Standard of Care (Control)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELAD SystemBiological
Also called ELAD
An extracorporeal human hepatic cell-based liver treatment
Standard of Care (Control)Other
Also called Standard of Care
Standard medical treatment as defined by the protocol
| Study group | Role | What they receive |
|---|---|---|
| ELAD System | Experimental | This group will receive treatment with ELAD plus standard of care therapy. Receives: Biological: ELAD System |
| Standard of Care (Control) | Other | This group will receive standard of care therapy as defined in the protocol. Receives: Other: Standard of Care (Control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Secondary outcomes (2)
Number of Survivors at Study Day 91
Assess the proportion of survivors at Study Day 91
Measured: Up to Study Day 91
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)
Measured: Up to Study Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2018
- Study completionSep 2018
Why it stopped: VTL-308 failed to meet its primary endpoint, all follow up studies were terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vital Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jan Stange, MD, Study director, Vital Therapies, Inc.David Reich, MD, Principal investigator, PA - Drexel UniversityLance Stein, MD, Principal investigator, GA - Piedmont Atlanta HospitalNikolaos Pyrsopoulos, MD, Principal investigator, NJ - Rutgers University HospitalValentin Cuervas-Mons, MD, Principal investigator, Spain - Hospital Universitario Puerta de Hierro MajadahondaRaza Malik, MD, Principal investigator, MA - Beth Israel Deaconess Medical CenterNikunj Shah, MD, Principal investigator, IL - Rush University Medical CenterSimona Rossi, MD, Principal investigator, PA - Albert Einstein Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02612428
- Sponsor's protocol ID
- VTL-308
- Status last verified
- Jan 2019
- First submitted
- 19 Nov 2015
- Last updated
- 25 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)
- ClinicalTrials.gov ID
- NCT02612428
- Acronym / sponsor ID
- VTL-308
- Conditions
- Acute Alcoholic Hepatitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: VTL-308 failed to meet its primary endpoint, all follow up studies were terminated
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Vital Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2016 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 23 Nov 2015 (estimated)
- Results
- Posted 25 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ELAD System | Experimental | Biological: ELAD SystemThis group will receive treatment with ELAD plus standard of care therapy. |
| Standard of Care (Control) | Other | Other: Standard of Care (Control)This group will receive standard of care therapy as defined in the protocol. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Age ≥18;
- Total bilirubin ≥16 mg/dL (≥273.6 µmol/L);
- 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;
- Maddrey score ≥32;
- Subjects must have AILD that is severe acute alcoholic hepatitis (sAAH) diagnosed with either:
Key exclusion criteria (42 listed)
- Age ≥50;
- Platelet count <40,000/mm3;
- International Normalization Ratio (INR) >2.5;
- Serum Creatinine ≥1.3 mg/dL (≥115.04 µmol/L);
- MELD score ≥30;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ELAD SystemAlso: ELADAn extracorporeal human hepatic cell-based liver treatment | Biological | ELAD System |
| Standard of Care (Control)Also: Standard of CareStandard medical treatment as defined by the protocol | Other | Standard of Care (Control) |
Primary outcome
Overall Survival
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).
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).
2 secondary outcomes
Number of Survivors at Study Day 91
Time frame: Up to Study Day 91
Number of Subjects With Early Change in Bilirubin Levels at Study Day 7
Time frame: Up to Study Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Company websiteLink provided by the sponsor.
Related trials for Acute Alcoholic Hepatitis
RecruitingPhase 2
A-TANGO Phase 2 Study
Acute-On-Chronic Liver Failure, Alcoholic Hepatitis
RecruitingObservational study
Integrative Epidemiology of Prognosis in Patients With Acute Alcoholic Hepatitis at AP-HP
Acute Alcoholic Hepatitis
Recruiting
Intestinal Microbiota Profiling in Severe Acute Alcoholic Hepatitis Patients
Severe Acute Alcoholic Hepatitis, Alcohol
Not yet recruitingPhase 2
MRG-001 in Patients With Alcoholic Hepatitis
Alcoholic Hepatitis, Acute Alcoholic Hepatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Stange, MD study director
Vital Therapies, Inc.
David Reich, MD principal investigator
PA - Drexel University
Lance Stein, MD principal investigator
GA - Piedmont Atlanta Hospital
44 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ELAD System in people with Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 44 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, United Kingdom, Spain, Germany, Austria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2019.