Acute-On-Chronic Liver FailurePhase 1NCT05727722
Micro-encapsulated Hepatocyte Intraperitoneal Transplantation in Liver Failure Adults
A Phase 1 study testing a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy in people with Acute-On-Chronic Liver Failure and Chronic Liver Failure, run by RenJi Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure, Chronic Liver Failure
- What is being tested?
- a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2024to 28 Feb 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
- Complicated with ascites and/or hepatic encephalopathy within 4 weeks after being diagnosed;
- Progressive aggravation of jaundice, total serum bilirubin≥85umol/L；
- Coagulation disorders, INR>1.5 or PTA<40%;
- No obvious improvement after more than 3 days' regular clinical treatments.
Who cannot join
- 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;
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- 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;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Qiang Xia, MD, PhD, +86-21-58752345, xiaqiang@shsmu.edu.cn
Ping Wan, MD, PhD, +86-15721069636, gufeng182@126.com
About this study
Official title: A Phase I Safety and Tolerability Dose Escalation Study of Micro-encapsulated Hepatocytes Intraperitoneal Transplantation Therapy for Adult Liver Failure Patients.
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.
Read the 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.
- Being tested
- a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy
- Keywords
- Acute-On-Chronic Liver Failure, Chronic Liver Failure, cell transplantation, hepatocyte transplantation, micro-encapsulate
- Medical subject headings
- Acute-On-Chronic Liver Failure, End Stage Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: baseline to 60 days after cell transplantation therapy
Secondary outcomes (4)
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.
Measured: baseline to 60 days after cell transplantation therapy
The survival rates compared with historical controls
The life table method was used to calculate the survival rate of patients.
Measured: the 60th day after cell transplantation therapy
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.
Measured: baseline to 60 days after cell transplantation therapy
Incidence of Clinical improvement
diagnosed refer to Chapter 2.6.2.2 of Guidelines for the Diagnosis and Management of Liver Failure (2018, China).
Measured: baseline to 60 days after cell transplantation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start1 Mar 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Institute of Biochemistry and Cell Biology
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05727722
- Sponsor's protocol ID
- IIT02-ProliHH-I
- Status last verified
- Jun 2025
- First submitted
- 23 Nov 2022
- Last updated
- 27 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40233953
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety and Tolerability Dose Escalation Study of Micro-encapsulated Hepatocytes Intraperitoneal Transplantation Therapy for Adult Liver Failure Patients.
- ClinicalTrials.gov ID
- NCT05727722
- Acronym / sponsor ID
- IIT02-ProliHH-I
- Keywords
- Acute-On-Chronic Liver Failure, Chronic Liver Failure, cell transplantation, hepatocyte transplantation, micro-encapsulate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- Shanghai Institute of Biochemistry and Cell Biology
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 14 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 1 | Experimental | Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyParticipants will each be administered the dosage of 0.15×10^9 for one time, with 60 days follow-up after the cell infusion. |
| Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 2 | Experimental | Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyParticipants will each be administered the dosage of 0.5×10^9 for one time, with 60 days follow-up after the cell infusion. |
| Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 3 | Experimental | Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyParticipants will each be administered the dosage of 1.5×10^9 for one time, with 60 days follow-up after the cell infusion. |
| Micro-encapsulated Hepatocyte Intraperitoneal Transplantation Cohort 4 | Experimental | Biological: a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyParticipants will each be administered the dosage of 4.5×10^9 for one time, with 60 days follow-up after the cell infusion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Chronic liver failure (CLF) group:
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapyA 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. | Biological | 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 |
Primary outcome
Incidence of Adverse events
Time frame: baseline to 60 days after cell transplantation therapy
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)
Maximum tolerated dose (MTD)
Time frame: baseline to 60 days after cell transplantation therapy
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.
4 secondary outcomes
Model for end-stage liver disease (MELD) score system
Time frame: baseline to 60 days after cell transplantation therapy
The survival rates compared with historical controls
Time frame: the 60th day after cell transplantation therapy
Serum antibodies against human leukocyte antigen (HLA) Class I and II
Time frame: baseline to 60 days after cell transplantation therapy
Incidence of Clinical improvement
Time frame: baseline to 60 days after cell transplantation therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Derived from this study: PubMed 40233953Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing a single course of micro-encapsulated hepatocytes intraperitoneal transplantation therapy in people with Acute-On-Chronic Liver Failure and Chronic Liver Failure, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse events (time frame: baseline to 60 days after cell transplantation therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05727722, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.