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

NCT ID: NCT02612428

Last Updated: 2019-01-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-09-30

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.

Conditions

Acute Alcoholic Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ELAD System

This group will receive treatment with ELAD plus standard of care therapy.

Group Type: EXPERIMENTAL

ELAD System

Intervention Type: BIOLOGICAL

An extracorporeal human hepatic cell-based liver treatment

Standard of Care (Control)

This group will receive standard of care therapy as defined in the protocol.

Group Type: OTHER

Standard of Care (Control)

Intervention Type: OTHER

Standard medical treatment as defined by the protocol

Interventions

ELAD System

An extracorporeal human hepatic cell-based liver treatment

Intervention Type: BIOLOGICAL

Standard of Care (Control)

Standard medical treatment as defined by the protocol

Intervention Type: OTHER

Other Intervention Names

ELAD; Standard of Care

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vital Therapies, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Stange, MD

Role: STUDY_DIRECTOR

Vital Therapies, Inc.

David Reich, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Drexel University

Lance Stein, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Piedmont Atlanta Hospital

Nikolaos Pyrsopoulos, MD

Role: PRINCIPAL_INVESTIGATOR

NJ - Rutgers University Hospital

Valentin Cuervas-Mons, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Puerta de Hierro Majadahonda

Raza Malik, MD

Role: PRINCIPAL_INVESTIGATOR

MA - Beth Israel Deaconess Medical Center

Nikunj Shah, MD

Role: PRINCIPAL_INVESTIGATOR

IL - Rush University Medical Center

Simona Rossi, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Albert Einstein Medical Center

Juan Caballeria, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Clinic de Barcelona

Ram Subramanian, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Emory University Hospital

Andres Duarte-Rojo, MD

Role: PRINCIPAL_INVESTIGATOR

AR - University of Arkansas for Medical Sciences

Julie Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

MN - University of Minnesota

Peter R Galle, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Universitätsmedizin Mainz

Hartmut H.-J. Schmidt, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Universitätsklinikum Münster

Markus Busch, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Medizinische Hochschule Hannover

Kristina Chacko, MD

Role: PRINCIPAL_INVESTIGATOR

NY - Montefiore Medical Center

Talal Adhami, MD

Role: PRINCIPAL_INVESTIGATOR

OH - Cleveland Clinic Foundation

Constance Mobley, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

TX - Houston Methodist Hospital

David J Kramer, MD

Role: PRINCIPAL_INVESTIGATOR

WI - Aurora St. Luke's Medical Center

Stephen Caldwell, MD

Role: PRINCIPAL_INVESTIGATOR

VA - University of Virginia Health System

Ali Al-Khafaji, MD

Role: PRINCIPAL_INVESTIGATOR

PA - University of Pittsburgh Medical Center

Kalyan R Bhamidimarri, MD

Role: PRINCIPAL_INVESTIGATOR

FL - Schiff Center for Liver Diseases/University of Miami

Manuel Romero-Gomez, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Virgen del Rocío

Tarek Hassanein, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Sharp Coronado Hospital

Waldo Concepcion, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Stanford University Medical Center

Martin Prieto Castillo, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario y Politécnico La Fe

Rafael Bañares, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Gregorio Marañón

Syed Naqvi, MD

Role: PRINCIPAL_INVESTIGATOR

MO - University of Missouri Hospital

Matthias Dollinger, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Germany - Klinikum Landshut gemeinnuetzige GmbH

Karen Krok, MD

Role: PRINCIPAL_INVESTIGATOR

PA - The Pennsylvania State University and The Milton S. Hershey Medical Center

Rudolf Stauber, MD

Role: PRINCIPAL_INVESTIGATOR

Austria - Medizinische Universität Graz

Christian Zauner, MD

Role: PRINCIPAL_INVESTIGATOR

Austria - Medizinische Universität Klinik Für Innere Medizin III

Georg Lamprecht, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Universitätsmedizin Rostock

Paul Thuluvath, MD

Role: PRINCIPAL_INVESTIGATOR

MD - Mercy Medical Center

Trinidad Serrano Aullo, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Clínico Universitario Lozano Blesa

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Sharp Coronado Hospital

Coronado, California, United States

Stanford University Medical Center

Palo Alto, California, United States

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Mercy Medical Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

University of Missouri Hospital

Columbia, Missouri, United States

Rutgers University Hospital

Newark, New Jersey, United States

Montefiore Medical Center

The Bronx, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The Pennsylvania State University and The Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Drexel University

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Medizinische Universität Graz

Graz, Styria, Austria

Medizinische Universität Klinik Für Innere Medizin III

Vienna, , Austria

Klinikum Landshut gemeinnuetzige GmbH

Landshut, Bavaria, Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

St. Vincent's University Hospital

Dublin, , Ireland

Hospital Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Aintree University Hospital

Liverpool, England, United Kingdom

Ninewells Hospital and Medical School

Dundee, Scotland, United Kingdom

Glasgow Royal Infirmary

Glasgow, Scotland, United Kingdom

Belfast Health and Social Care Trust

Belfast, , United Kingdom

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Doncaster Royal Infirmary

Doncaster, , United Kingdom

Royal London Hospital

London, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Nottingham University Hospital

Nottingham, , United Kingdom

Countries

United States; Austria; Germany; Ireland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://vitaltherapies.com

Company website

Other Identifiers

VTL-308

Identifier Type: -

Identifier Source: org_study_id