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

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

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.

Study Overview

• Status: Terminated
• Conditions: Liver Transplantation
• Intervention / Treatment: Biological: LIV-GAMMA SN Inj.; Other: No intervention

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Jai Young Cho, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Nam-Joon Yi, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Dong Jin Joo, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Jong Man Kim, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Chung-Ang University Hospital
    • Contact: Suk-Won Suh, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Ewha Womans University Seoul Hospital
    • Contact: Geun Hong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• Others whom the investigator considers ineligible for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; LIV-GAMMA SN Inj. administration after ABO-incompatible liver transplantation	Biological: LIV-GAMMA SN Inj.; 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.
Other: Comparator group; No administration after ABO-incompatible liver transplantation	Other: No intervention; None of investigational drugs are administered to patients.
Other: Reference group; No administration after ABO-compatible liver transplantation	Other: No intervention; None of investigational drugs are administered to patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of biliary complications	The number and rate of subjects with biliary complications including cholangitis, biliary leaks or biliary strictures for 48 weeks after liver transplantation (Experimental group vs. Comparator group)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of transplant rejection	The number and rate of subjects with transplant rejection for 48 weeks after liver transplantation	48 weeks
Rate of Donor Specific Antibody (DSA)	The number and rate of subjects with Donor Specific Antibody (DSA) for 48 weeks after liver transplantation	48 weeks
Rate of antibody reaction by ABO subtype	The number and rate of subjects with antibody reaction by ABO subtype analysis for 48 weeks after liver transplantation	48 weeks
Rate of Cytomegalovirus (CMV) infection	The number and rate of subjects with Cytomegalovirus (CMV) infection for 48 weeks after liver transplantation	48 weeks
Rate of infectious complications	The number and rate of subjects with infectious complications for 48 weeks after liver transplantation	48 weeks
Rate of Diffuse Intrahepatic Biliary Stricture (DIHBS)	The number and rate of subjects with Diffuse Intrahepatic Biliary Stricture (DIHBS) for 48 weeks after liver transplantation	48 weeks
Recurrence rate of Hepatocellular Carcinoma (HCC)	The recurrence rate of subjects with Hepatocellular Carcinoma (HCC) for 48 weeks after liver transplantation	48 weeks

Collaborators and Investigators

• Sponsor: SK Plasma Co., Ltd.
• Investigators: Study Chair: Nam-Joon Yi, MD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: December 17, 2022
• First Submitted That Met QC Criteria: December 17, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: SK_LIV_ABO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No