Micro-encapsulated Hepatocyte Intraperitoneal Transplantation in Liver Failure Adults
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorRenJi Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Sequential
Treatments tested in this trial
a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy
Biological/VaccineA 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.
Treatment groups
10 Participants
are divided into 4 treatment groupsGroup A: Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 1Experimental treatment 1 intervention
Group B: Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 2Experimental treatment 1 intervention
Group C: Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 3Experimental treatment 1 intervention
Group D: Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 4Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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)
Time frame
baseline to 60 days after cell transplantation therapy2
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.
Time frame
baseline to 60 days after cell transplantation therapySecondary outcomes
1
Model for end-stage liver disease (MELD) score system
Laboratory test results used to calculate the MELD score must be obtained at the same time point, and the results need to be obtained within 6 hours of the blood draw.
Time frame
baseline to 60 days after cell transplantation therapy2
The survival rates compared with historical controls
The life table method was used to calculate the survival rate of patients.
Time frame
the 60th day after cell transplantation therapy3
Serum antibodies against human leukocyte antigen (HLA) Class I and II
The serum antibodies against HLA Class I and II are used to for immunogenicity evaluation.
Time frame
baseline to 60 days after cell transplantation therapy4
Incidence of Clinical improvement
diagnosed refer to Chapter 2.6.2.2 of Guidelines for the Diagnosis and Management of Liver Failure (2018, China).
Time frame
baseline to 60 days after cell transplantation therapySponsors and contacts
Click on the lead sponsor to view all of their trials.
RenJi Hospital
Lead sponsor
Shanghai Institute of Biochemistry and Cell Biology
Collaborator
Source ClinicalTrials.gov