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

NCT02612428 | Terminated Phase 3 Results DMC

• 1 other identifier: VTL-308
• Study Type: interventional
• Target: 151
• Locations: 6 countries
• Sites: 44

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.

Conditions

Acute Alcoholic Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  Up to Study Day 91

• Number of Subjects With Early Change in Bilirubin Levels at Study Day 7

  Up to Study Day 7

Study Arms (2)

ELAD System

EXPERIMENTAL

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

Biological: ELAD System

Standard of Care (Control)

OTHER

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

Other: Standard of Care (Control)

Interventions

ELAD System BIOLOGICAL

An extracorporeal human hepatic cell-based liver treatment

Also known as: ELAD

ELAD System

Standard of Care (Control) OTHER

Standard medical treatment as defined by the protocol

Also known as: Standard of Care

Standard of Care (Control)

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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:
• 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:
• i. 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.

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Vital Therapies, Inc.: lead

Study Sites (44)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Sharp Coronado Hospital

Coronado, California, 92118, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Missouri Hospital

Columbia, Missouri, 65212, United States

Location

Rutgers University Hospital

Newark, New Jersey, 07101, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

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

Hershey, Pennsylvania, 17033, United States

Location

Drexel University

Philadelphia, Pennsylvania, 19102, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Medizinische Universität Graz

Graz, Styria, 8036, Austria

Location

Medizinische Universität Klinik Für Innere Medizin III

Vienna, 1090, Austria

Location

Klinikum Landshut gemeinnuetzige GmbH

Landshut, Bavaria, 84034, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Münster

Münster, D-48149, Germany

Location

Universitätsmedizin Rostock

Rostock, D-18065, Germany

Location

St. Vincent's University Hospital

Dublin, Dublin 4, Ireland

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Aintree University Hospital

Liverpool, England, L97AL, United Kingdom

Location

Ninewells Hospital and Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, Scotland, G40SF, United Kingdom

Location

Belfast Health and Social Care Trust

Belfast, BT9 7AB, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, DN2 5LT, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Nottingham University Hospital

Nottingham, NG7 2UH, United Kingdom

Location

Related Links

• Company website

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Robert Ashley, Chief Technical Officer
• Organization: Vital Therapies, Inc.

rashley@vitaltherapies.com

001 858-673-6840

Study Officials

• Jan Stange, MD

  Vital Therapies, Inc.

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 23, 2015
• Study Start: January 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: September 1, 2018
• Last Updated: January 25, 2019
• Results First Posted: January 25, 2019

Record last verified: 2019-01

Locations

AU (2); DE (5); IE (1); US (21); ES (6); GB (9)