Clinical Study of Hepatocyte Transplantation for Liver Cirrhosis

Shanghai Jiao Tong University

Status and phase: Not yet enrolling; Phase 1

Conditions: Liver Cirrhosis

Treatments: Drug: Allogeneic Hepatocyte

Study type: Interventional

Funder types: Other

Identifiers

NCT04806581

HI-IM-001

Details and patient eligibility

About

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.

Full description

• 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).

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 3 patient groups

Allogeneic Hepatocyte Cohort 1

Experimental group

Description:

Participants will each be administered L dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: L

Treatment:

Drug: Allogeneic Hepatocyte

Allogeneic Hepatocyte Cohort 2

Experimental group

Description:

Participants will each be administered M dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: M

Treatment:

Drug: Allogeneic Hepatocyte

Allogeneic Hepatocyte Cohort 3

Experimental group

Description:

Participants will each be administered H dose for one time. With 28days follow-up after the cells infusion. Allogeneic hepatocyte cell numbers: H

Treatment:

Drug: Allogeneic Hepatocyte