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Clinical Trial Results:
A Randomized, Open-label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD® in Subjects with Alcohol-Induced Liver Decompensation (AILD).

Summary
EudraCT number	2015-004529-14
Trial protocol	ES DE IE AT
Global end of trial date	14 Sep 2018

Results information
Results version number	v1(current)
This version publication date	13 Jan 2019
First version publication date	13 Jan 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
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Trial information

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Sponsor protocol code

VTL-308

ISRCTN number

US NCT number

NCT02612428

WHO universal trial number (UTN)

Sponsor organisation name

Vital Therapies, Inc.

Sponsor organisation address

15010 Avenue of Science, San Diego, United States, 92128

Public contact

EVP & Chief Technical Officer, Robert A. Ashley, Vital Therapies, Inc., 001 520289 3236, rashley@vitaltherapies.com

Scientific contact

EVP & Chief Technical Officer, Robert A. Ashley, Vital Therapies, Inc., 001 520289 3236, rashley@vitaltherapies.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Aug 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Jun 2018

Global end of trial reached?

Yes

Global end of trial date

14 Sep 2018

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of the study is to evaluate safety and efficacy of ELAD® with respect to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) through at least Study Day 91, with follow-up Protocol VTL-308E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTL-308 study termination (after the last surviving enrolled subject completes Study Day 91). The primary objective will be assessed using a Kaplan-Meier survival analysis of the Intent-to-Treat (ITT) population utilizing a log-rank test.

Protection of trial subjects

Continuous monitoring of the ELAD System by trained ELAD Specialists during ELAD treatment. Administration of diphenhydramine or equivalent immediately prior to initiation of ELAD treatment to prevent hypersensitivity reactions.

Background therapy

The majority of subjects with AILD present with clinical characteristics of alcoholic hepatitis (AH). The Standard of Care (background therapy) for the secondary medical problems associated with AH was derived from the practice guidelines issued by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of Liver (EASL). These guidelines were applied to both the ELAD-treated and Control subjects during this study.

Evidence for comparator

VTL-308 was a randomized, multicenter, open-label, concurrent control study of subjects with AILD. Subjects meeting the eligibility requirements of the study received either standard of care treatment for AILD (as defined in the protocol) plus treatment with the ELAD System (ELAD group) or standard of care treatment for AILD alone (Control group). Treatment options for patients with AILD are limited. The majority of subjects with AILD present with clinical characteristics of AH. Patients with severe AH (defined as a Maddrey Discriminant Function of ≥32) have a poor prognosis, with 90-day survival of around 50%. Regimens that have been used for the past 40 years, including corticosteroids, theophylline with corticosteroids, pentoxifylline, and infliximab, have had no significant effect on the long term survival of patients with AILD. Of particular importance are the results of the UK NIHR-supported STOPAH study, a study in alcoholic hepatitis reporting out in 2015. Results from this study, which randomized 1103 subjects in 40 clinical sites in the UK, showed that the administration of steroids and pentoxifylline had no effect on survival at 90 days either alone or in combination. While a sham control is a potential comparator, regulatory and ethical bodies have determined that the administration of a sham extracorporeal therapy without the possibility of benefit is unethical, and therefore could not be considered for study VTL-308. Consequently, the best available standard of care in accord with AASLD and EASL guidelines was recommended in the VTL-308 study protocol for all participants irrespective of treatment arm.

Actual start date of recruitment

16 May 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country