A Clinical Study to Evaluate the Efficacy and Safety of LIV-GAMMA SN Inj. in ABO-Incompatible Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of LIV-GAMMA SN Inj. administered for consecutive 3 days in adult subjects to prevent biliary complications after ABO incompatible adult to adult living donor liver transplantation (LDLT). The primary objective of this study is to determine the incidence rate of biliary complications for 48 weeks after liver transplantation. Incidence rate of transplant rejection, DSA, antibody reaction, CMV infection, infectious complications, DIHBS and recurrence rate of HCC as well as adverse events are assessed as additional efficacy and safety endpoints in this study.

Official Title
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A Multi-center, Prospective, Randomized, Controlled, Open-label, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of IVIg to Prevent Biliary Complications After ABO-Incompatible Living Donor Liver Transplantation

Conditions
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Liver Transplantation

Intervention / Treatment
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* Biological: LIV-GAMMA SN Inj.
* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed informed consent process Male or female aged ≥19 years and <75 years Patients scheduled hospitalization for liver transplantation Exclusion Criteria: Patients who are scheduled or have history of re-transplantation or multiorgan transplantation Patients receiving living donor in emergency Patients with Donor Specific Antibody (DSA) ≥ MFI 10,000 or Human Leukocyte Antigen (HLA) crossmatch (+) cytotoxic T-cell ≥ 1:32 Patients with a history of biliary tract disease Patients who plasma exchange is forbidden (with a history of allergic or anaphylactic reaction to FFP, albumin, heparin, etc.) Patients with a history of specific medical conditions Severe renal failure (eGFR < 30 mL/min/1.73 m^2 at screening) Deep Vein Thrombosis (DVT) or thrombotic complications from Intravenous Immunoglobulin (IVIg) therapy Cerebrovascular or cardiovascular disease (Hyperviscosity syndrome, Transient Ischemic Attack (TIA), Stroke, Thromboembolism, Unstable angina, etc.) Clinical state causing secondary immunodeficiency (Leukemia, Lymphoma, Multiple myeloma, HIV infection, Chronic or Cyclic neutropenia (Absolute neutrophil < 500/mm^3), etc.) Uncontrolled hypertension (Systolic blood pressure > 160 mmHg or Diastolic blood pressure > 100 mmHg) Hemolytic or hemorrhagic anemia Decreased cardiac functions Bacterial, fungal or viral infection making liver transplantation forbidden Intraductal or vascular infiltration observed in patients with hepatocellular carcinoma using medical imaging before liver transplantation Patients metastasized to organs except for liver or diagnosed cancer except for liver cancer and squamous cell carcinoma within 5 years from screening Patients with sepsis Patients who had interventional therapy in blood vessels (hepatic vein, portal vein, hepatic artery, etc.) or bile ducts before LDLT Patients who have allergy or hypersensitivity to blood products, blood-derived products, IVIg or immunoglobulin G (IgG) products Patients who have immunoglobulin A (IgA) deficiency or anti-IgA antibody Patients who are pregnant and nursing Patients unwilling to use adequate method of contraception (hormonal methods, intrauterine device or intrauterine system, vasectomy, tubal ligation, etc.) during this study Patients who had received other investigational products within 8 weeks from complete consent or who are scheduled to receive other investigational products during this study

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>LIV-GAMMA SN Inj. administration after ABO-incompatible liver transplantation | Biological: LIV-GAMMA SN Inj.<br>* LIV-GAMMA SN Inj. is administered at a dose of 0.6 g/kg/day from anhepatic phase to Day 2 post-operative to patients undergoing ABO-incompatible liver transplantation as an experimental group.<br>|
| Other: Comparator group<br>No administration after ABO-incompatible liver transplantation | Other: No intervention<br>* None of investigational drugs are administered to patients.<br>|
| Other: Reference group<br>No administration after ABO-compatible liver transplantation | Other: No intervention<br>* None of investigational drugs are administered to patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of biliary complications | Number of participants with and rate of biliary complications including cholangitis, biliary leaks or biliary strictures for 48 weeks after liver transplantation (Experiment group vs. Comparator group) | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of transplant rejection | Number of participants with and rate of transplant rejection for 48 weeks after liver transplantation | 48 weeks | 
| Rate of Donor Specific Antibody (DSA) | Number of participants with and rate of Donor Specific Antibody (DSA) for 48 weeks after liver transplantation | 48 weeks | 
| Rate of antibody reaction by ABO subtype | Number of participants with and rate of antibody reaction by ABO subtype for 48 weeks after liver transplantation | 48 weeks | 
| Rate of Cytomegalovirus (CMV) infection | Number of participants with and rate of Cytomegalovirus (CMV) infection for 48 weeks after liver transplantation | 48 weeks | 
| Rate of infectious complications | Number of participants with and rate of infectious complications for 48 weeks after liver transplantation | 48 weeks | 
| Rate of Diffuse Intrahepatic Biliary Stricture (DIHBS) | Number of participants with and rate of Diffuse Intrahepatic Biliary Stricture (DIHBS) for 48 weeks after liver transplantation | 48 weeks | 
| Recurrence rate of Hepatocellular Carcinoma (HCC) | Number of participants with and recurrence rate of Hepatocellular Carcinoma (HCC) for 48 weeks after liver transplantation | 48 weeks | 
| Adverse event | Number of participants with and rate of adverse event during this study | 48 weeks |