The study examines the safety and efficacy of ELAD treatment as acontinuous liver support to a subject with compromised liver functionowing to severe acute alcoholic hepatitis who are Lille score failures (Lille score >0.45), allowing time for the subject's native liver to regenerate to a healthy state. The primary objective is to evaluate safety and efficacy with respect to overall survival of subjects through study termination (after last surviving enrolled subject completes Study Day 91).

Phase 1

• Conditions: Severe Acute Alcoholic Hepatitis (sAAH); MedDRA version: 18.0Level: PTClassification code 10019755Term: Hepatitis chronic activeSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2013-001884-21-GB
• Lead Sponsor: VITAL THERAPIES INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-11
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Subjects must meet ALL inclusion criteria to be eligible for the study:

1. Age = 18 years;

2. Total bilirubin = 8 mg/dL;

3. Medical history of alcohol abuse with evidence of a causal and
temporal (<6 weeks) relationship to the use of alcohol and hospital admission for this episode of sAAH;

4. Maddrey score of = 32;

5. A clinical diagnosis of severe acute alcoholic hepatitis (sAAH) defined as meeting two or more of the following:

a. Hepatomegaly,
b. AST > ALT,
c. Ascites,
d. Leukocytosis (WBC count above lab normal at site)

6. Subject must have either:

a. A liver biopsy that, in the Investigator’s opinion, confirms a
diagnosis of sAAH (stratum A);

OR

b. In the Investigator’s opinion, a liver biopsy is not justified due to
the risk versus the diagnostic value, and no confirmatory liver
biopsy is available, in which case the clinical diagnosis is
sufficient (stratum B);

7. Subject must be a Lille score failure(Lille score > 0.45) as defined in this study;

8. Subject must be eligible for Standard of Care treatment as defined in protocol;

9. Subject or legally authorized representative must provide Informed Consent for all phases of the study (Treatment and 5-year Follow-Up
Registry).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

Subjects must NOT have any of the following exclusion criteria:
1. Platelet count < 50,000/mm3;
2. International Normalization Ratio (INR) > 3.0;
3. MELD Score > 35;
4. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom, etc.) indicated by any of the following:
a. Presence of sepsis or septic shock; OR
b. Positive blood cultures (Bacteremia, Fungemia) within 72 hours prior to Randomization; OR
c. Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization
d. Clinical and radiological signs of pneumonia;
5. Evidence of jaundice for >3 months;
6. Hospital admission for any other episodes of liver decompensation not related to sAAH (other than this episode of sAAH) within the past 2 months;
7. Evidence of hemodynamic instability as defined by the following:
a. Systolic blood pressure < 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
b. Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
c. Requirement for escalating doses of vasopressor support prior to Screening; OR
d. Subject at maximum vasopressor dose at Screening or Randomization (low doses are allowed); low dose vasopressor doses are defined as:
Dobutamine: Low doses: 2.5 to 5.0 µg/kg/min
Dopamine: Low doses: 0.5 to 2 µg/kg/min
Norepinephrine: Low doses: 0.01 to 0.02 µg/kg/min
Phenylephrine: Low doses: 0.05 to 1 µg/kg/min
Vasopressin: Low doses: 0.01 to 0.02 U/min
8. Either clinical evidence of active bleeding, or of a major haemorrhage. Major haemorrhage is defined as requiring = 2 units packed red blood cells to maintain a stable haemoglobin occurring within 48 hours of Screening;
9. Evidence of occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;
10. Evidence by physical exam, history, or laboratory evaluation of significant concomitant disease with expected life expectancy of less than 3 months, including but not limited to:
a. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
b. Cancer that has metastasized or has not yet been treated;
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, CT or MRI or liver volume < 750 cc as determined by CT or MRI], unless Investigator interpretation of the clinical evidence indicates liver size of < 10 cm or volume < 750 cc is not considered reduced for the individual subject;
12. Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
13. Uncontrolled seizures;
14. Positive serologies for viral hepatitis B (HBsAg) or hepatitis C indicating acute/chronic chronic infection or a positive viral load for either hepatitis B or C;
15. Pregnancy as determined by ß-human chorionic gonadotropin (HCG) results;
16. 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-210 clinical trial);
17. Currently listed or schedule

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified