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

Acute-On-Chronic Liver Failure Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03882346
• Other study ID #: LC-BAL-18
• Status: Recruiting
• Phase: Phase 2
• Start date: March 29, 2019
• Est. completion date: June 2022

Study information

• Verified date: April 2020
• Source: HLB Cell Co., Ltd.
• Contact: Younyoung Hwang
• Phone: +82-2-2627-6773
• Email: yy.hwang[@]hlb-bio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Liver Failure
• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure
• Liver Failure, Acute

Intervention

Combination Product:
• LifeLiver
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.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
HLB Cell Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival rate for 30 days	To compare survival rate of LifeLiver treatment with best supportive care	up to 30 days
Primary	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	up to approximately 12 months
Primary	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.	up to approximately 12 months
Secondary	Survival rate for 14 days	To compare survival rate of LiveLiver treatment with best supportive care	up to 14 days
Secondary	Median value of duration of survival	To compare Median value of duration of survival between experimental group and control group	up to approximately 12 months
Secondary	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	up to 30 days
Secondary	Kaplan-Meier estimate of subjects with 31= MELD score =37	To compare Kaplan-Meier estimate of both groups at 14 days and 30 days	up to 30 days
Secondary	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)	up to approximately 12hours after completion of LifeLiver treatment
Secondary	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)	up to approximately 12 hours after completion of LifeLiver treatment
Secondary	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)	up to approximately 12 hours after completion of LifeLiver treatment
Secondary	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	up to approximately 12 hours after completion of LifeLiver treatment
Secondary	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-a, Interleukin-6, Interleukin-10)	up to approximately 12 hours after completion of LifeLiver treatment