The Safety and Tolerability Study of HepaCure in Chinese Subjects With Acute-On-Chronic Liver Failure

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, controlled, open-label phase 1/2 clinical study conducted in China to evaluate the efficacy, safety and tolerability of hiHep cell-based bio-artificial liver support system (HepaCure) plus DPMAS versus DPMAS alone in Chinese subjects with acute-on-chronic liver failure（ACLF）. Phase 1 is a multicenter, open label study to evaluate the safety and tolerability of single dose and multiple doses of HepaCure with different treatment duration plus DPMAS in ACLF subjects respectively.

Official Title
-----------------
A Multicenter, Randomized, Controlled, Open-Label Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability and Efficacy of HepaCure Plus DPMAS Versus DPMAS Alone in Chinese Subjects With Acute-On-Chronic Liver Failure

Conditions
-----------------
Acute on Chronic Hepatic Failure, Liver Failure, Hepatitis

Intervention / Treatment
-----------------
* Combination Product: HepaCure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to communicate effectively with investigators and sign the informed consent form (ICF) voluntarily. Age: ≥ 18 years and ≤ 65 years. Body weight: ≥ 40kg; Met the criteria of ACLF in the early and middle stages in screening period (Guidelines for the Diagnosis and Treatment of Liverfilture (2018 Edition)): base on chronic liver disease, acute jaundice deepened and coagulation dysfunction caused by various inducements, manifested as extreme fatigue, with obvious gastrointestinal symptoms such as anorexia, vomiting, abdominal distention, etc; Progressive deepening of jaundice, serum TBil ≥ 171 μmol/L or increase ≥ 17.1 μmol/L daily; with bleeding tendencies or manifestations (bleeding spots or ecchymosis), or 20%<PTA ≤ 40% (or 1.5 ≤ INR<2.6), and other reasons excluded. Exclusion Criteria: Subjects with primary or metastatic liver cancer. Subjects with severe esophageal/gastric varices and high risk of bleeding, with positive red signs, or with previous active bleeding, as indicated by gastroscopy or imaging examination results. Pneumonia refer to the diagnostic criteria of the American Society of Infectious Diseases/American Thoracic Society for adult severe pneumonia in 2007), abdominal infection (after reasonable antibiotic treatment, there are still Peritonitis manifestations or white blood cells in ascites>0.1 × 10 9/L), etc. Subjects with serious uncontrolled infections, including sepsis, septic shock, severe pneumonia (refers to the diagnostic criteria of the American Society of Infectious Diseases/American Thoracic Society for adult severe pneumonia in 2007), abdominal infection (exist Peritonitis manifestations or white blood cells in ascites>0.1 × 10 9/L after reasonable antibiotic treatment), etc;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HepaCure<br>Patients will receive Hepacure treatment on top of DPMAS | Combination Product: HepaCure<br>* HepaCure will be administered in extracorporal dialysis for single dose or multiple doses with different treatment duration on top of DPMAS.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety outcome | The adverse events (AE), Serious adverse event (SAE), adverse events of special concern (AESI), and device defects (leakage caused by the quality problem of the plasma biological purification column itself) of the safety paramater will be collected, and the safety and tolerability within 14 days and 28 days will be evaluated from the end of the last treatment | 28 days after the end of last treatment |