Study to Evaluate Safety and Efficacy of LifeLiver in Acute or Acute-on-Chronic Liver Failure Patients

April 27, 2020 updated by: HLB Cell Co., Ltd.

A Phase 2b Study to Evaluate Safety and Efficacy of LifeLiver (Bio Artificial Liver) in Acute or Acute-on-Chronic Liver Failure Patients Waiting Emergent Liver Transplantation

This is a prospective, comparative, open label, phase 2b study designed to investigate the safety and efficacy of LifeLiver (an Extracorporeal Bio Artificial Liver). The study will recruit approximately 40 acute or acute-on-chronic liver failure patients.

Study Overview

Detailed Description

Patient should have acute or acute-on-chronic liver failure and be registered in KONOS (Korean Network for Organ Sharing) system as a candidate of liver transplantation. Patients who meet the eligibility criteria will be assigned to control group or experimental group. Experimental group patients will receive LifeLiver treatment in addition to the best supportive care for the disease.

Primary Objective:

1. To evaluate the efficacy of LifeLiver in terms of a comparison of 30 day-survival rate between control group and experimental group. (after patient's KONOS (Korean Network for Organ Sharing) registration date)

Secondary Objective:

  1. To compare a median value of 2 week-survival rate and duration of survival between both study groups
  2. Survival analysis respect to each group of patients divided according to the KONOS status
  3. To investigate safety and change of overall efficacy indicators in terms of Glasgow Coma Scale, West Heaven Criteria for hepatic encephalopathy, MELD (Model for End-stage Liver Disease) score, blood ammonia, inflammatory cytokine

Study Type

Interventional

Enrollment (Anticipated)

40

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 Contact

Study Contact Backup

Study Locations

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

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 to 60 years of age
  • Acute or acute-on-chronic liver failure patients who is waiting for liver transplantation (KONOS liver transplant emergency grade 2 or 3)
  • Hepatic encephalopathy grade II or above
  • The following laboratory values must be documented within the screening period:

    • INR (international normalized ratio) 2.0 or above
    • Serum ammonia 56 micromole/L or above
    • Total bilirubin 5mg/dL or above
    • Body weight 45kg or above
  • Patient who can not expect effective treatment or prolonged survival
  • Patient or patient's legal representative willing to provide informed consent and commit to study procedures

Exclusion Criteria:

  • Patient who has contraindication to plasmapheresis
  • Severe hypotension (systolic blood pressure 80mmHg or less)
  • Platelet < 15,000/mm3
  • Contraindications to liver transplantation (sepsis, severe heart disease, uncontrollable hemorrhage, irreversible brain damage)
  • Cerebral hemorrhage
  • Positive HIV infection
  • Serious or life-threatening hemorrhage just before initiation of the study
  • Patients with high gastrointestinal bleeding tendency (a history or suspicion of gastrointestinal bleeding within last 3 months)
  • Hepatocellular carcinoma patient with 7 (or more) tumors or a 6cm (or larger) diameter single tumor
  • Pregnant or lactating women
  • Antibiotics (beta-lactam family) hypersensitive and streptomycin, amphotericin B sensitive patients
  • Patients with inappropriate condition to participate the study under investigator's judgement

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control Group
Patients in Control Group will receive best supportive care for the disease.
Experimental: Experimental Group
Patients in Experimental Group will receive LifeLiver treatment in addition to best supportive care for the disease.
LifeLiver is an extracorporeal bioartificial liver (BAL) system. The system has shown remarkable detoxification capacity and sustained hepatic functions and also provides a bridge to transplant for patients who are unable to receive timely liver transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival rate for 30 days
Time Frame: up to 30 days
To compare survival rate of LifeLiver treatment with best supportive care
up to 30 days
Occurrence of clinical safety laboratory adverse events (AEs)
Time Frame: up to approximately 12 months
To compare occurrence of clinical safety laboratory adverse events between Experimental group and Control group assessed according to NCI-CTCAE v5.0
up to approximately 12 months
Incidence of transition of PERV (Porcine Endogenous Retrovirus) (for experimental group only)
Time Frame: up to approximately 12 months
Number of reported PERV transition defined as viral detection in subject's blood by PCR (Polymerase Chain Reaction) test.
up to approximately 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival rate for 14 days
Time Frame: up to 14 days
To compare survival rate of LiveLiver treatment with best supportive care
up to 14 days
Median value of duration of survival
Time Frame: up to approximately 12 months
To compare Median value of duration of survival between experimental group and control group
up to approximately 12 months
Kaplan-Meier estimate of subjects with MELD (Modell for End-stage Liver Disease) score >37
Time Frame: up to 30 days
To compare Kaplan-Meier estimate of both (experimental and control) groups at 14 days and 30 days
up to 30 days
Kaplan-Meier estimate of subjects with 31≤ MELD score ≤37
Time Frame: up to 30 days
To compare Kaplan-Meier estimate of both groups at 14 days and 30 days
up to 30 days
Comparison of MELD score
Time Frame: up to approximately 12hours after completion of LifeLiver treatment
Intra-group comparison (between pre and post 12 hours of LifeLiver treatment) and Inter-group comparison (between both groups) of subject's MELD score (range of minimum 6 to maximum 40)
up to approximately 12hours after completion of LifeLiver treatment
Comparison of subject's neurological status - hepatic encephalopathy grade
Time Frame: up to approximately 12 hours after completion of LifeLiver treatment
Intra-group comparison (between pre and post 12 hours of LifeLiver treatment) and Inter-group comparison (between both groups) of subject's hepatic encephalopathy grade (range of minimum 1 to maximum 4)
up to approximately 12 hours after completion of LifeLiver treatment
Comparison of subject's neurological status - Glasgow Coma Scale
Time Frame: up to approximately 12 hours after completion of LifeLiver treatment
Intra-group comparison (between pre and post 12 hours of LifeLiver treatment) and Inter-group comparison (between both groups) of subject's Glasgow Coma Scale (range of minimum 3 to maximum 15)
up to approximately 12 hours after completion of LifeLiver treatment
Comparison of subject's value of blood ammonia
Time Frame: up to approximately 12 hours after completion of LifeLiver treatment
Intra-group comparison (between pre and post 12 hours of LifeLiver treatment) and Inter-group comparison (between both groups) of subject's value of blood ammonia
up to approximately 12 hours after completion of LifeLiver treatment
Comparison of subject's value of inflammatory cytokines
Time Frame: up to approximately 12 hours after completion of LifeLiver treatment
Intra-group comparison (between pre and post 12 hours of LifeLiver treatment) and Inter-group comparison (between both groups) of subject's value of inflammatory cytokines (TNF-α, Interleukin-6, Interleukin-10)
up to approximately 12 hours after completion of LifeLiver treatment

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Dong Hyun Sinn, MD, Ph.D, Samsung Medical Center

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 (Actual)

March 29, 2019

Primary Completion (Anticipated)

March 1, 2022

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

March 13, 2019

First Submitted That Met QC Criteria

March 19, 2019

First Posted (Actual)

March 20, 2019

Study Record Updates

Last Update Posted (Actual)

April 28, 2020

Last Update Submitted That Met QC Criteria

April 27, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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