Back to resultsStudy to Evaluate Safety and Efficacy of LifeLiver in Acute or Acute-on-Chronic Liver Failure Patients
Primary Purpose
Acute Liver Failure, Acute-On-Chronic Liver Failure
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
LifeLiver
Sponsored by
About this trial
This is an interventional treatment trial for Acute Liver Failure focused on measuring Acute Liver Failure, Acute-On-Chronic Liver Failure, Artificial Liver, Liver Transplantation
Eligibility Criteria
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
Sites / Locations
- Samsung Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control Group
Experimental Group
Arm Description
Patients in Control Group will receive best supportive care for the disease.
Patients in Experimental Group will receive LifeLiver treatment in addition to best supportive care for the disease.
Outcomes
Primary Outcome Measures
Survival rate for 30 days
To compare survival rate of LifeLiver treatment with best supportive care
Occurrence of clinical safety laboratory adverse events (AEs)
To compare occurrence of clinical safety laboratory adverse events between Experimental group and Control group assessed according to NCI-CTCAE v5.0
Incidence of transition of PERV (Porcine Endogenous Retrovirus) (for experimental group only)
Number of reported PERV transition defined as viral detection in subject's blood by PCR (Polymerase Chain Reaction) test.
Secondary Outcome Measures
Survival rate for 14 days
To compare survival rate of LiveLiver treatment with best supportive care
Median value of duration of survival
To compare Median value of duration of survival between experimental group and control group
Kaplan-Meier estimate of subjects with MELD (Modell for End-stage Liver Disease) score >37
To compare Kaplan-Meier estimate of both (experimental and control) groups at 14 days and 30 days
Kaplan-Meier estimate of subjects with 31≤ MELD score ≤37
To compare Kaplan-Meier estimate of both groups at 14 days and 30 days
Comparison of MELD score
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)
Comparison of subject's neurological status - hepatic encephalopathy grade
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)
Comparison of subject's neurological status - Glasgow Coma Scale
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)
Comparison of subject's value of blood ammonia
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
Comparison of subject's value of inflammatory cytokines
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03882346
Brief Title
Study to Evaluate Safety and Efficacy of LifeLiver in Acute or Acute-on-Chronic Liver Failure Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 29, 2019 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
June 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HLB Cell Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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:
To compare a median value of 2 week-survival rate and duration of survival between both study groups
Survival analysis respect to each group of patients divided according to the KONOS status
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Liver Failure, Acute-On-Chronic Liver Failure
Keywords
Acute Liver Failure, Acute-On-Chronic Liver Failure, Artificial Liver, Liver Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a parallel, open label study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Patients in Control Group will receive best supportive care for the disease.
Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
Patients in Experimental Group will receive LifeLiver treatment in addition to best supportive care for the disease.
Intervention Type
Combination Product
Intervention Name(s)
LifeLiver
Intervention Description
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.
Primary Outcome Measure Information:
Title
Survival rate for 30 days
Description
To compare survival rate of LifeLiver treatment with best supportive care
Time Frame
up to 30 days
Title
Occurrence of clinical safety laboratory adverse events (AEs)
Description
To compare occurrence of clinical safety laboratory adverse events between Experimental group and Control group assessed according to NCI-CTCAE v5.0
Time Frame
up to approximately 12 months
Title
Incidence of transition of PERV (Porcine Endogenous Retrovirus) (for experimental group only)
Description
Number of reported PERV transition defined as viral detection in subject's blood by PCR (Polymerase Chain Reaction) test.
Time Frame
up to approximately 12 months
Secondary Outcome Measure Information:
Title
Survival rate for 14 days
Description
To compare survival rate of LiveLiver treatment with best supportive care
Time Frame
up to 14 days
Title
Median value of duration of survival
Description
To compare Median value of duration of survival between experimental group and control group
Time Frame
up to approximately 12 months
Title
Kaplan-Meier estimate of subjects with MELD (Modell for End-stage Liver Disease) score >37
Description
To compare Kaplan-Meier estimate of both (experimental and control) groups at 14 days and 30 days
Time Frame
up to 30 days
Title
Kaplan-Meier estimate of subjects with 31≤ MELD score ≤37
Description
To compare Kaplan-Meier estimate of both groups at 14 days and 30 days
Time Frame
up to 30 days
Title
Comparison of MELD score
Description
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)
Time Frame
up to approximately 12hours after completion of LifeLiver treatment
Title
Comparison of subject's neurological status - hepatic encephalopathy grade
Description
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)
Time Frame
up to approximately 12 hours after completion of LifeLiver treatment
Title
Comparison of subject's neurological status - Glasgow Coma Scale
Description
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)
Time Frame
up to approximately 12 hours after completion of LifeLiver treatment
Title
Comparison of subject's value of blood ammonia
Description
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
Time Frame
up to approximately 12 hours after completion of LifeLiver treatment
Title
Comparison of subject's value of inflammatory cytokines
Description
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)
Time Frame
up to approximately 12 hours after completion of LifeLiver treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Younyoung Hwang
Phone
+82-2-2627-6773
Email
yy.hwang@hlb-bio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Eunyoung Kim
Phone
+82-2-2627-6791
Email
ey.kim@hlb-bio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dong Hyun Sinn, MD, Ph.D
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanghoon Lee, MD, Ph.D
Phone
+82-2-3410-0928
Email
sanghoone.lee@samsung.com
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate Safety and Efficacy of LifeLiver in Acute or Acute-on-Chronic Liver Failure Patients
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