Clinical trial NCT05727722: Micro-encapsulated Hepatocyte Intraperitoneal Transplantation in Liver Failure Adults
Official title: A Phase I Safety and Tolerability Dose Escalation Study of Micro-encapsulated Hepatocytes Intraperitoneal Transplantation Therapy for Adult Liver Failure Patients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute-On-Chronic Liver Failure
Chronic Liver Failure
Keywords: Acute-On-Chronic Liver Failure
Chronic Liver Failure
cell transplantation
hepatocyte transplantation
micro-encapsulate
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Institute of Biochemistry and Cell Biology
First posted: 2023-02-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a prospective single-center dose escalation study of the administration of the microencapsulated hepatocyte therapy in adult liver failure. The purpose of the study is to determine the maximum tolerated dose of microencapsulated hepatocytes in liver failure patients and its effectiveness in treating the disease.

Detailed description: This study is a single-center unblinded single-arm study comprised of a dose escalation phase and a preliminary assessment of efficacy. Subjects who were diagnosed with liver failure (including chronic liver failure and acute-on-chronic liver failure) received 3 days' regular treatment with no beneficial effect and volunteered to participate in micro-encapsulated hepatocytes intraperitoneal transplantation therapy will be enrolled. Before the clinical research, the recruitment criteria and micro-encapsulated hepatocytes transplantation protocol will be confirmed. To minimize the number of patients receiving unbeneficial therapeutic dosage, the accelerated titration design and "3+3" design will be used to decide the dosage group. All micro-encapsulated hepatocytes transplantation patients will be monitored after 1, 3, 7, 14, 28, and 60 days after treatment for safety and primary efficacy analyses. The patients could still receive regular clinical treatment including liver transplantation.

Eligibility criteria: Inclusion Criteria:

A. Chronic liver failure (CLF) group:

The progressive liver function decline or decompensation after liver cirrhosis:

1. Body weight\>40kg;
2. Aged between 18 to 65 years old;
3. Serum Total bilirubin was higher than the normal range and lower than 10 times the upper limit of normal value (ULN);
4. With or without significantly decreased serum albumin value, lower than 35;
5. With or without significantly decreased platelet (PLT) value, prothrombin activity (PTA)≤40% (or international normalized ratio (INR)≥1.5), other reasons excluded;
6. With or without refractory ascites or portal hypertension;
7. With or without a stage I or II hepatic encephalopathy;
8. No obvious improvement after more than 3 days' regular clinical treatments.

OR B. Acute-on-chronic liver failure (ACLF) group:

With known or unknown basic liver diseases, subjects undergoing acute liver failure syndrome (clinical manifestations indicated as an early stage liver failure).

1. Body weight\>40kg;
2. Aged between 18 to 65 years old;
3. With obvious fatigue, accompanied by other gastrointestinal symptoms such as anorexia, vomiting, and abdominal distension;
4. Complicated with ascites and/or hepatic encephalopathy within 4 weeks after being diagnosed;
5. Progressive aggravation of jaundice, total serum bilirubin≥85umol/L；
6. Coagulation disorders, INR\>1.5 or PTA\<40%;
7. No obvious improvement after more than 3 days' regular clinical treatments.

Exclusion Criteria:

1. With obvious brain edema, cerebral hernia, or indicated intracranial hemorrhage;
2. Diagnosed or suspected as primary or metastatic liver cancer;
3. With uncorrectable oxygenation index (PaO2/FiO2)\<200;
4. With disseminated intravascular coagulation;
5. Active hemorrhage;
6. Uncontrollable infection, including ascites infection such as spontaneous bacterial peritonitis;
7. Uncorrectable decrease in PLT (\<20×109/L);
8. HIV and/or SARS-CoV-Ⅱ positive;
9. Drug abuse within 1 year;
10. Systemic hemodynamic instability;
11. Combined with pregnancy or lactation;
12. Other situations excluded by clinician;

Primary outcomes:
measure: Incidence of Adverse events
timeFrame: baseline to 60 days after cell transplantation therapy
measure: Maximum tolerated dose (MTD)
timeFrame: baseline to 60 days after cell transplantation therapy
Secondary outcomes:
measure: Model for end-stage liver disease (MELD) score system
timeFrame: baseline to 60 days after cell transplantation therapy
measure: The survival rates compared with historical controls
timeFrame: the 60th day after cell transplantation therapy
measure: Serum antibodies against human leukocyte antigen (HLA) Class I and II
timeFrame: baseline to 60 days after cell transplantation therapy
measure: Incidence of Clinical improvement
timeFrame: baseline to 60 days after cell transplantation therapy
Other outcomes:
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