Micro-encapsulated Hepatocyte Intraperitoneal Transplantation in Liver Failure Adults

NCT05727722 | Recruiting Phase 1

• 1 other identifier: IIT02-ProliHH-I
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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. We previously generated proliferating human hepatocytes (ProliHH) through dedifferentiation of PHH and engineered them into encapsulated liver organoids (eLO), providing an unlimited cell source for hepatocyte transplantation.

Conditions

Acute-On-Chronic Liver Failure; Chronic Liver Failure

Keywords

Acute-On-Chronic Liver Failure; Chronic Liver Failure; cell transplantation; hepatocyte transplantation; micro-encapsulate

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse events

  All adverse events are defined and graded following the National Cancer Institute-Common Terminology Criteria for Adverse Events V.5.0. Adverse events (AE), serious adverse events (SAE), and treatment emergent AEs (TEAE)

  baseline to 60 days after cell transplantation therapy

• Maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) is defined as the highest dose at which no more than 1 of at least 6 subjects developed dose-limiting toxicity (DLT). During the DLT observation period, another patient should be enrolled if one subject does not complete the DLT observation period due to withdrawal for reasons other than DLT.

  baseline to 60 days after cell transplantation therapy

Secondary Outcomes (4)

• Model for end-stage liver disease (MELD) score system

  baseline to 60 days after cell transplantation therapy

• The survival rates compared with historical controls

  the 60th day after cell transplantation therapy

• Serum antibodies against human leukocyte antigen (HLA) Class I and II

  baseline to 60 days after cell transplantation therapy

• Incidence of Clinical improvement

  baseline to 60 days after cell transplantation therapy

Study Arms (4)

Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 1

EXPERIMENTAL

Participants will each be administered the dosage of 0.15×10\^9 for one time, with 60 days follow-up after the cell infusion.

Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy

Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 2

EXPERIMENTAL

Participants will each be administered the dosage of 0.5×10\^9 for one time, with 60 days follow-up after the cell infusion.

Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy

Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 3

EXPERIMENTAL

Participants will each be administered the dosage of 1.5×10\^9 for one time, with 60 days follow-up after the cell infusion.

Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy

Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 4

EXPERIMENTAL

Participants will each be administered the dosage of 4.5×10\^9 for one time, with 60 days follow-up after the cell infusion.

Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy

Interventions

a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy BIOLOGICAL

A single course will be divided into an "accelerated titration design" phase and a "3+3 design" phase to reduce the number of subjects exposed to potentially ineffective doses that may not benefit from treatment. The "accelerated titration design" phase starts at a starting dose of 0.15x10\^9, moving to the "3+3 design" phase at the dose of 0.5x10\^9. According to the semi-logarithmic incremental (10\^0.5-fold) approach, the treatment dosage was set into four groups at a maximum dose of 4.5×10\^9 (allowing for a ±20% difference between the actual dose and the planned dose, considering production specifics). The number or the incremental ratio of subsequent dose groups can be adjusted based on the evaluation of available data in the study, and intermediate doses can be explored.

Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 1; Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 2; Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 3; Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Chronic liver failure (CLF) group:
• The progressive liver function decline or decompensation after liver cirrhosis:
• Body weight\>40kg;
• Aged between 18 to 65 years old;
• Serum Total bilirubin was higher than the normal range and lower than 10 times the upper limit of normal value (ULN);
• With or without significantly decreased serum albumin value, lower than 35;
• With or without significantly decreased platelet (PLT) value, prothrombin activity (PTA)≤40% (or international normalized ratio (INR)≥1.5), other reasons excluded;
• With or without refractory ascites or portal hypertension;
• With or without a stage I or II hepatic encephalopathy;
• 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).
• Body weight\>40kg;
• Aged between 18 to 65 years old;
• With obvious fatigue, accompanied by other gastrointestinal symptoms such as anorexia, vomiting, and abdominal distension;

You may not qualify if:

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

Sponsors & Collaborators

• RenJi Hospital: lead
• Shanghai Institute of Biochemistry and Cell Biology: collaborator

Study Sites (1)

Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

RECRUITING

Related Publications (1)

• Yang T, Zhu X, Long M, Hui L, Yuan X, Sun Z, Zhang L, Xia Q, Wan P. Phase I safety and tolerability dose escalation study of microencapsulated hepatocyte intraperitoneal transplantation therapy in adult patients with liver failure: a study protocol. BMJ Open. 2025 Apr 15;15(4):e087828. doi: 10.1136/bmjopen-2024-087828.

  PMID: 40233953 DERIVED

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; End Stage Liver Disease

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: February 14, 2023
• Study Start: March 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: February 28, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

CN (1)