Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)

January 22, 2019 updated by: Vital Therapies, Inc.

An Open-Label, Multicenter, Historically-Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Acute Liver Failure (ALF)

This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls.

Study Overview

Detailed Description

The VTI-212 study (VTI-212) is an open-label, multicenter, historically-controlled study of subjects with acute liver failure (ALF). Approximately 40 subjects who meet the eligibility requirements of the study will receive ELAD treatment in addition to standard of care treatment for ALF. The outcomes of these subjects will be compared with matched historical controls drawn from existing databases.

Subjects will undergo ELAD treatment for a minimum of 3 days (72 hours). It is recommended ELAD treatment be continued up to 10 days (240 hours).

Following ELAD treatment, subjects will continue standard medical therapy as defined by the institution and be followed through Study Day 28.

Subjects' diagnosis of ALF will be attributed to one of the following:

  1. Fulminant Hepatic Failure (FHF) (acute liver failure with no preexisting liver disease);
  2. Primary Graft Non-Function (PNF);
  3. Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery.

Screening evaluations and assessments will be completed for subjects and reviewed against inclusion/exclusion criteria.

Enrollment will define the time of study entry (Hour 0, Study Day 1, study baseline) and inclusion in the Intent-to-treat (ITT) population. Subjects will be evaluated throughout the 28-day study period.

If standard medical therapy, as defined by the institution and this protocol is consistent with discharging the subject home, then the subject should be discharged. Prior to discharge, the subject will be advised to attend all follow-up visits.

An extension of this study, the VTI-212E study (VTI-212E), will provide additional ELAD survival data, as available, through VTI-212 study termination (after the last surviving enrolled ELAD subject completes Study Day 28). This registry protocol segment of VTI-212 extends the safety monitoring period to 5 years to assess survival, incidence and characterization of tumor (in particular hepatocellular tumor), incidence of liver transplant, and assess quality of life using a standard, validated questionnaire.

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 Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90033
        • Keck Hospital of USC
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Hospital
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Floriday
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30309
        • Piedmont Atlanta Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center - Twin Cities Campus
    • New Jersey
      • Newark, New Jersey, United States, 07102
        • Rutgers University Hospital
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • New York, New York, United States, 10016
        • New York University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
    • Texas
      • Dallas, Texas, United States, 75203
        • Methodist Dallas Medical Center - The Liver Institute
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Weight ≥ 40 kg;
  2. Age ≥ 18;
  3. Diagnosis of ALF attributed to one of the following:

    1. FHF (acute liver failure with no preexisting liver disease, see below);
    2. Primary Graft Non-Function (PNF);
    3. Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery);
  4. Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours;
  5. Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E.

    Subjects with FHF must meet one of the following criteria:

  6. Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:

    1. Prothrombin time (PT) > 100 seconds [International Normalized Ratio (INR) > 6.5], OR
    2. Encephalopathy Grade 3 or 4 AND ARTERIAL AMMONIA >100 umol/liter and at least one of the following:

    i. Arterial pH < 7.30 at ≥ 24 hours after drug ingestion or volume resuscitation; ii. Renal failure documented by urine output < 0.5 mL/kg/hr over the preceding 12 hours; iii. Creatinine > 2.5 mg/dL; OR

  7. Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia >100 umol/liter, and at least two of the following:

    1. Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF
    2. Serum bilirubin > 17 mg/dL
    3. Subject > 40 years old
    4. PT > 50 seconds (INR > 3.5)
    5. Jaundice to encephalopathy time ≥ 7 days

Exclusion Criteria:

  1. Cerebral Perfusion Pressure ≤40 mm Hg for 1 hour or longer as measured by an intracranial pressure (ICP) monitor. (NOTE: In those cases where ICP monitor placement cannot be performed prior to study enrollment, this exclusion criterion will not apply);
  2. Chronic liver disease (e.g., compensated cirrhosis of any etiology, chronic hepatitis, nonalcoholic steatohepatitis, cholestatic liver disease, or metabolic liver disease) (NOTE: steatosis is not an exclusion criterion);
  3. Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;
  4. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) 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 Enrollment; OR
    3. Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR
    4. Clinical and radiological signs of pneumonia.
  5. Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer (except non-melanoma skin cancer), acute fatty-liver disease, hepatitis due to herpes virus or Budd-Chiari syndrome. (NOTE: in the case of subjects enrolled due to surgery-induced liver failure (SILF) then the original cause for the surgery will not be a criterion for exclusion);
  6. Portal hypertension;
  7. Liver dysfunction due to trauma;
  8. Irreversible brain death;
  9. Platelet count < 30,000/mm3 [NOTE: Subject may be included at the physician's discretion if platelet count exceeds 30,000/mm3 at time of initiation of therapy (even if the value is following platelet transfusion) and can be managed through the administration of blood products]
  10. Cardiovascular sepsis-related organ failure assessment score (SOFA score) >3;
  11. Stroke or intracranial hemorrhage;
  12. Seizures uncontrolled by medication;
  13. Acute myocardial infarction;
  14. Lung disease defined by a partial pressure of oxygen measurement (PaO2) ≤60 mmHg or a fraction of inspired oxygen (FiO2) ≥0.6, not corrected by medical management [including continuous venovenous hemofiltration (CVVH) if indicated] and ventilation with a Positive End Expiratory Pressure (PEEP) of >8cm H2O;
  15. Acute Respiratory Distress Syndrome;
  16. Pregnancy as determined by beta-human chorionic gonadotropin (β-hCG) results;
  17. ≤ 2 weeks postpartum;
  18. 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 VTI-212 clinical trial);
  19. Prior ELAD therapy;
  20. Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or local equivalent) or any other Advanced Directive limiting Standard of Care in place (the DNR/DNI criterion is not applicable in the UK).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ELAD plus standard of care
Continuous ELAD treatment for a minimum of 3 days to a maximum of 10 days in addition to a standard of care for subjects with acute liver failure.
Continuous treatment with the ELAD System for a minimum of 3 days to a maximum of 10 days. The subject's ultrafiltrated blood is circulated through 4 cartridges, each containing approximately 110 grams of C3A cells (approximately 440 grams total).
Other Names:
  • Human Cell-Based Bio-Artificial Liver Support System

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall Survival (OS) of ALF Subjects
Time Frame: Study Day 1 through Study Day 28
Study Day 1 through Study Day 28

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Subjects Who Survived at the End of Study Day 28 or Who Received Orthotopic Liver Transplantation on or Before That Study Day.
Time Frame: Study Day 1 through Study Day 28
Study Day 1 through Study Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paul J Gaglio, MD, NY - Montefiore Medical Center
  • Principal Investigator: Xaralambos Zervos, DO, FL - Cleveland Clinic Florida
  • Principal Investigator: Nikolaos T Pyrsopoulos, MD, NJ - Rutgers University Hospital
  • Study Chair: Jan Stange, MD, Ph.D., Vital Therapies, Inc.
  • Principal Investigator: Parvez Mantry, MD, TX - Methodist Dallas Medical Center - The Liver Institute
  • Principal Investigator: Juan Gallegos-Orozco, MD, UT - University of Utah
  • Principal Investigator: Lewis W Teperman, MD, NY - New York University Medical Center
  • Principal Investigator: Winfred W Williams, Jr., MD, MA - Massachusetts General Hospital
  • Principal Investigator: Marquis Hart, MD, WA - Swedish Medical Center
  • Principal Investigator: Linda S Sher, MD, CA - Keck Hospital of USC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2018

Study Registration Dates

First Submitted

June 5, 2013

First Submitted That Met QC Criteria

June 7, 2013

First Posted (Estimate)

June 12, 2013

Study Record Updates

Last Update Posted (Actual)

February 12, 2019

Last Update Submitted That Met QC Criteria

January 22, 2019

Last Verified

January 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Liver Failure

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