A Phase 2 Study of GC1102 (Recombinant Hepatitis B Immunoglobulin) in HBV-related Liver Transplant Recipients

A Randomized, Open-label, Single-center, Phase II Trial to Explore the Safety and Efficacy of GC1102 and Determine Its Optimal Dose After Intravenous Administration in HBV-related Liver Transplant Recipients

This is a proof-of-concept study for GC1102 to demonstrate preventing the recurrence of hepatitis B virus (HBV) infection following liver transplantation and a dose-finding study to determine its optional dose.

Study Overview

• Status: Completed
• Conditions: Hepatitis B Infection
• Intervention / Treatment: Biological: GC1102 50,000 IU; Biological: GC1102 80,000 IU

Detailed Description

GC1102 is a new recombinant hepatitis B immunoglobulin (HBIg) from Chinese Hamster Ovary (CHO) cells. It is a monoclonal antibody and has high affinity and avidity to hepatitis B surface antigen and several advantages compared to HBIg derived from blood plasma of human donors. Forty volunteers will participate in the study, receive 24-week treatment with low dose (50,000IU) of GC1102 or with high dose (80,000IU) and be followed up till 28 weeks.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul ASAN Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Given written informed consent
• Aged 19 - 65 years
• Expected liver transplantation related to hepatitis B
• Positive HBsAg

Exclusion Criteria:

• Patients has participated in any other clinical trial within 30 days
• Patients who are scheduled re-operation for liver transplantation
• Patients with are co-infected with HAV, HCV or HIV
• History of malignant tumor within 5 years except primary liver cancer
• Patients with moderate or severe renal disorder (serum creatinine > 1.5 X ULM) or anuria, acute renal failure or dialysis
• Patients who had experienced cardiovascular attack, myocardiac infarction, PTCA or coronary bypass or with angina, arrhythmia, or any other clinically meaningful valvular heart disease, cerebral infarction or cerebral hemorrhage within 6 months
• History of anaphylaxis against active ingredient or excipients of study drug
• Patients who had been vaccinated with parenteral live vaccine (measles vaccine, epidemic parotitis vaccine, rubella vaccine, cholera vaccine, chickenpox vaccine) within 3 months
• Patients who had been treated with any other immuno globulin within 3 months
• Pregnant or breast-feeding women
• Women of childbearing potential who do not agree to use appropriate contraceptive methods (condom, an intrauterine device, oral contraceptive hormones, or a vasectomy of male sex partner) during this study
• Alcohol or drug abuse within 6 months
• Patients who has any clinically meaningful disease in investigator's judgement to prevent participating in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GC1102 50,000 IU; Anhepatic phase: 50,000 IU intravenous during surgery, Post-transplantation(1st week): 50,000 IU intravenous every day, Post-transplantation(2nd-4th weeks): 50,000 IU intravenous every weeks, Post-transplantation(8th weeks and till 24 weeks): 50,000 IU intravenous every 4 weeks.	Biological: GC1102 50,000 IU; a recombinant hepatitis B immunoglobulin
Experimental: GC1102 80,000 IU; Anhepatic phase: 80,000 IU intravenous during surgery, Post-transplantation(1st week): 80,000 IU intravenous every day, Post-transplantation(2nd-4th weeks): 80,000 IU intravenous every weeks, Post-transplantation(8th weeks and till 24 weeks): 80,000 IU intravenous every 4 weeks.	Biological: GC1102 80,000 IU; a recombinant hepatitis B immunoglobulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate of Hepatitis B	Seroconversion rate of HBsAg or HBeAg	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rate of HBsAg or HBeAg		28 weeks
Seroconversion time of HBsAg or HBeAg		28 weeks
Overall survival rate		28 weeks
Geometric mean titer (GMT) of HBV DNA		Day 6, 28, 59, 84, 112, 140, 158, 196
Histological findings of hepatic graft	if available	Baseline
Incidence rate of Anti-GC1102 Antibody		28 weeks
Mutation rate of HBV DNA		28 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events		28 weeks
Clinical abnormalities in physical exam, vital signs, and/or laboratory		28 weeks
Infusion reactions	Any adverse events occurred within 72 hours after intervention	72 hours
Pharmacokinetic parameters of GC1102 titer (C trough, t 1/2b, AUC, C max, and T max)	C trough, t 1/2b, AUC, C max, and T max	Day 6, 28, 59, 84, 112, 140, 158, 196

Collaborators and Investigators

• Sponsor: Green Cross Corporation
• Investigators: Principal Investigator: Sung-Gyu Lee, M.D., Seoul ASAN Medical Center; Study Director: Chang-Hee Lee, M.D., GC Biopharma Corp

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: November 26, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 1, 2014

Study Record Updates

• Last Update Posted (Estimate): June 30, 2016
• Last Update Submitted That Met QC Criteria: June 29, 2016
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: HBV-related liver transplantation; Hepatitis B Immuno Globulin
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: GC1102_P2