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Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects w/ AILD

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ClinicalTrials.gov Identifier: NCT02612428
Recruitment Status : Active, not recruiting
First Posted : November 23, 2015
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.

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.


Condition or disease Intervention/treatment Phase
Acute Alcoholic Hepatitis Biological: ELAD System Other: Standard of Care (Control) Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 2016
Actual Primary Completion Date : March 2018
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: ELAD System
This group will receive treatment with ELAD plus standard of care therapy.
Biological: ELAD System
An extracorporeal human hepatic cell-based liver treatment
Other Name: ELAD

Standard of Care (Control)
This group will receive standard of care therapy as defined in the protocol.
Other: Standard of Care (Control)
Standard medical treatment as defined by the protocol
Other Name: Standard of Care




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 91 days ]
    Overall survival will be assessed using a Kaplan-Meier analysis of the Intent-to-Treat population, utilizing a log-rank test


Secondary Outcome Measures :
  1. Proportion of survivors [ Time Frame: 91 days ]
    A chi-square test will be used to evaluate the proportion of subjects who survived at end of study day 91



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 exclusion criteria to be eligible for the study:

  1. Age ≥50;
  2. Platelet count <40,000/mm3;
  3. International Normalization Ratio (INR) >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:

    1. Presence of sepsis or septic shock; OR
    2. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Randomization; OR
    3. Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization; OR
    4. 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:

    1. Systolic blood pressure <90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
    2. Mean arterial pressure (MAP) <60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
    3. Requirement for escalating doses of vasopressor support prior to Screening; OR
    4. 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:

    1. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
    2. Cancer that has metastasized or has not yet been treated;
    3. 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 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;
  19. 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;
  20. 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);
  21. Previous liver transplant;
  22. Previous enrollment in the treatment phase of another ELAD trial;
  23. 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);
  24. Refusal to participate in the VTL-308E follow-up study;
  25. Inability to provide an address for home visits.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02612428


  Hide Study Locations
Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Sharp Coronado Hospital
Coronado, California, United States, 92118
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Florida
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Piedmont Atlanta Hospital
Atlanta, Georgia, United States, 30309
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
University of Missouri Hospital
Columbia, Missouri, United States, 65212
United States, New Jersey
Rutgers University Hospital
Newark, New Jersey, United States, 07101
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
The Pennsylvania State University and The Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Drexel University
Philadelphia, Pennsylvania, United States, 19102
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Wisconsin
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Austria
Medizinische Universität Graz
Graz, Styria, Austria, 8036
Medizinische Universität Klinik Für Innere Medizin III
Vienna, Austria, 1090
Germany
Klinikum Landshut gemeinnuetzige GmbH
Landshut, Bavaria, Germany, 84034
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Universitätsmedizin Mainz
Mainz, Germany, 55131
Universitätsklinikum Münster
Münster, Germany, D-48149
Universitätsmedizin Rostock
Rostock, Germany, D-18065
Ireland
Belfast Health and Social Care Trust
Belfast, Ireland, BT9 7AB
St. Vincent's University Hospital
Dublin, Ireland, Dublin 4
Spain
Hospital Puerta de Hierro Majadahonda
Majadahonda, Madrid, Spain, 28222
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Hospital Universitario y Politécnico La Fe
Valencia, Spain, 46026
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain, 50009
United Kingdom
Aintree University Hospital
Liverpool, England, United Kingdom, L97AL
Ninewells Hospital and Medical School
Dundee, Scotland, United Kingdom, DD1 9SY
Glasgow Royal Infirmary
Glasgow, Scotland, United Kingdom, G40SF
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2GW
Doncaster Royal Infirmary
Doncaster, United Kingdom, DN2 5LT
Royal London Hospital
London, United Kingdom, E1 1BB
Royal Free Hospital
London, United Kingdom, NW3 2QG
Nottingham University Hospital
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Study Director: Jan Stange, MD Vital Therapies, Inc.
Principal Investigator: David Reich, MD PA - Drexel University
Principal Investigator: Lance Stein, MD GA - Piedmont Atlanta Hospital
Principal Investigator: Nikolaos Pyrsopoulos, MD NJ - Rutgers University Hospital
Principal Investigator: Valentin Cuervas-Mons, MD Spain - Hospital Universitario Puerta de Hierro Majadahonda
Principal Investigator: Raza Malik, MD MA - Beth Israel Deaconess Medical Center
Principal Investigator: Nikunj Shah, MD IL - Rush University Medical Center
Principal Investigator: Simona Rossi, MD PA - Albert Einstein Medical Center
Principal Investigator: Juan Caballeria, MD Spain - Hospital Clinic de Barcelona
Principal Investigator: Ram Subramanian, MD GA - Emory University Hospital
Principal Investigator: Andres Duarte-Rojo, MD AR - University of Arkansas for Medical Sciences
Principal Investigator: Julie Thompson, MD MN - University of Minnesota
Principal Investigator: Peter R Galle, MD Germany - Universitätsmedizin Mainz
Principal Investigator: Hartmut H.-J. Schmidt, MD Germany - Universitätsklinikum Münster
Principal Investigator: Markus Busch, MD Germany - Medizinische Hochschule Hannover
Principal Investigator: Kristina Chacko, MD NY - Montefiore Medical Center
Principal Investigator: Talal Adhami, MD OH - Cleveland Clinic Foundation
Principal Investigator: Constance Mobley, MD, PhD TX - Houston Methodist Hospital
Principal Investigator: David J Kramer, MD WI - Aurora St. Luke's Medical Center
Principal Investigator: Stephen Caldwell, MD VA - University of Virginia Health System
Principal Investigator: Ali Al-Khafaji, MD PA - University of Pittsburgh Medical Center
Principal Investigator: Kalyan R Bhamidimarri, MD FL - Schiff Center for Liver Diseases/University of Miami
Principal Investigator: Manuel Romero-Gomez, MD Spain - Hospital Universitario Virgen del Rocío
Principal Investigator: Tarek Hassanein, MD CA - Sharp Coronado Hospital
Principal Investigator: Waldo Concepcion, MD CA - Stanford University Medical Center
Principal Investigator: Martin Prieto Castillo, MD Spain - Hospital Universitario y Politécnico La Fe
Principal Investigator: Rafael Bañares, MD Spain - Hospital Universitario Gregorio Marañón
Principal Investigator: Syed Naqvi, MD MO - University of Missouri Hospital
Principal Investigator: Matthias Dollinger, MD, PhD Germany - Klinikum Landshut gemeinnuetzige GmbH
Principal Investigator: Karen Krok, MD PA - The Pennsylvania State University and The Milton S. Hershey Medical Center
Principal Investigator: Rudolf Stauber, MD Austria - Medizinische Universität Graz
Principal Investigator: Christian Zauner, MD Austria - Medizinische Universität Klinik Für Innere Medizin III
Principal Investigator: Georg Lamprecht, MD Germany - Universitätsmedizin Rostock
Principal Investigator: Paul Thuluvath, MD MD - Mercy Medical Center
Principal Investigator: Trinidad Serrano Aullo, MD Spain - Hospital Clínico Universitario Lozano Blesa

Additional Information:
Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT02612428     History of Changes
Other Study ID Numbers: VTL-308
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders