Clinical Study of Hepatocyte Transplantation for Liver Cirrhosis

Study Overview
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Brief Summary
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The Primary Objective: To observe and determine the safety and tolerance of allogeneic hepatocyte transplantation in patients with liver cirrhosis and to establish the maximum-tolerated dose (MTD) and evaluate the dose-limiting toxicities (DLTs). The Secondary Objective: To observe the therapeutic efficacy of allogeneic hepatocyte transplantation for liver cirrhosis.

Detailed Description
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A traditional 3 + 3 dose escalation design will be implemented. Successive cohorts of participants (3 or 3+3 participants /cohort) will start on a fixed cell numbers of allogeneic hepatocyte in three cohorts separately: L dose (low cell numbers); M dose (medium cell numbers); H dose (high cell numbers). The 1st cohort will be given dose of L. The 2nd cohort will be given dose of M. The 3rd cohort will be given dose of H. Dose escalation will continue until the maximum-tolerated dose (MTD). If no DLTs are observed for 28days after administration of the last dose, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in 2 of the three participants, the MTD will be determined to be the dose administered to the previous cohort. If DLTs are observed in one participant in the cohort, another three participants will be treated with the same dose level. If the new three participants aren't observed DLTs, another cohort will be enrolled at the upper dose. If at least one of the new three ones are observed DLTs, the below dose will be the MTD. MTD will stopped by testing increasing up to the H dose. Toxicities will be graded using the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).

Official Title
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Clinical Study of Congener Allogeneic Hepatocyte Transplantation Treatment in Patients With Liver Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: Allogeneic Hepatocyte


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The age at the time of signing the informed consent from 18 to 70 years old (including the boundary value), both male and female; Clinical diagnosis of liver cirrhosis; Be able to understand and sign informed consent. Key Exclusion Criteria: Combined with liver cancer or other malignant tumors; Patients who can't cooperate; Prothrombin time (PT) exceeded the upper limit of normal control for 3-5 seconds or more; International normalized ratio (INR) >1.5; PLT<60×109/L； Recently use of anticoagulant or antiplatelet drugs (last 7 days); Recently (last 4 weeks) had upper gastrointestinal bleeding or spontaneous celiac inflammation; Moderate or large amount of ascites; The investigator assesses that the patient is unable or unwilling to comply with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Hepatocyte Cohort 1<br>Participants will each be administered L dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: L | Drug: Allogeneic Hepatocyte<br>* Allogeneic hepatocyte with cell numbers L,M,H respectively.<br>|
| Experimental: Allogeneic Hepatocyte Cohort 2<br>Participants will each be administered M dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: M | Drug: Allogeneic Hepatocyte<br>* Allogeneic hepatocyte with cell numbers L,M,H respectively.<br>|
| Experimental: Allogeneic Hepatocyte Cohort 3<br>Participants will each be administered H dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: H | Drug: Allogeneic Hepatocyte<br>* Allogeneic hepatocyte with cell numbers L,M,H respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | Observe the safety and tolerance after single infusion of hepatocyte. | 28days | 
| Dose-Limiting Toxicities | Observe the safety and tolerance after single infusion of hepatocyte. | 28days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver cirrhosis; allogeneic hepatocyte; transplantation