A Phase 1 Study of GC1102 (Recombinant Hepatitis B Immunoglobulin) in Chronic Hepatitis B Patients

A Prospective, Open-label, Dose-escalation, Single-center, Phase I Trial to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of GC1102 (Recombinant Hepatitis B Human Immunoglobulin)

This study is SAD(Single Ascending Dose)/MAD(Multiple Ascending Dose) study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of GC1102 (Recombinant Hepatitis B Human Immunoglobulin) in Chronic Hepatitis B Patients.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: GC1102

Detailed Description

GC1102 is a new recombinant hepatitis B human immunoglobulin. This study is composed with 2 Parts, Part A for SAD and Part B for MAD and total 4 dosing program which is escalated after confirming safety. Maximum 48 subjects will be participated in the study.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with chronic hepatitis B or those who diagnosed with chronic hepatitis B carrier who given written informed consent.
• Patients aged ≥19 and ≤ 65 years
• If Naïve for the Nucleos(t)ide analogs therapy, HBeAg (-), HBsAg 1,000 IU/mL or less and HBV DNA 2,000IU/mL or less Or If currently receiving Nucleos(t)ide analogs therapy, HBeAg (±), HBsAg 1,000 IU/mL or less and HBV DNA (-: limit of detection of 60 IU/mL or less).

Exclusion Criteria:

• Patients who currently involved or has participated in any other clinical trial within 30 days.
• Patients co-infected with HAV, HCV or HIV
• Patients with history of malignant tumor within 5 years except basal cell carcinoma of skin, cervical intraepithelial neoplasia.
• Patients who have active infection except chronic hepatitis infection.
• Patients with liver disease who had complications such as gastroesophageal variceal, ascites and hepatic encephalopathy.
• Having eGFR 59 mL/min/1.73m2 or less with MDRD Evaluation phase (moderate reduction in GFR or more )
• Having blood or protein 1+ or more by the urine analysis with microscopic examination.
• Patients who have a clinically significant kidney disease including glomerulonephritis, anuria, acute renal failure, dialysis and renal transplantation.
• Patients with Vasculitis.
• Having leukocytes <3.0 x109/L
• Having Absolute Neutrophil Count<1.5x109/L
• Having platelet <750,000/mm3 during screening
• Having hemoglobin <10g/dL
• Having positive sign of serum cryoglobulin level.
• Having serum anti-nuclear antibody (ANA) 1:160 or more
• Patients who showed positive sign of serum perinuclear anti-Neutrophil Cytoplasmic Antibodies (p-ANCA).
• Patients who showed positive sign of serum cytoplasmic anti-Neutrophil Cytoplasmic Antibodies (c-ANCA).
• Patients who had history or be suspected of immune disease
• Patients who had experienced cardiovascular attack, myocardiac infarction, heart failure, PTCA or coronary artery bypass, angina, arrhythmia, any other clinically meaningful valvular heart disease, cerebral infarction or cerebral hemorrhage within 6 months.
• Patients who had history of anaphylaxis against the main component or subcomponent of study drug.
• Patients who had been administered live vaccine parentally (measles vaccine, parotitis vaccine, rubella vaccine, cholera combined vaccine, varicella vaccine) within 3 months prior to the dosing of study drug.
• Patients who had been received an immunosuppressant, immunity-modifying drug including interferon agents, cytotoxic chemotherapy that can affect their immune system, or radiation therapy within 3 months prior to the dosing of study drug
• Patients who had been treated with any other immunoglobulin within 3 months prior to the dosing of study drug
• Patients who had been treated with systemic steroid Therapy(more than 20 mg/day of prednisolone or its equivalence administered every day for more than 14 days, or more than 700 mg of a cumulative dose during the same period of time) within 3 months prior to the dosing of study drug (topical administration such as topical ointments, eye drops, inhalants or intranasal use, intra-articular injection, or tendon injection is acceptable; alternative-day treatment is acceptable even though administered for more than 14 days)
• Women who showed positive sign of pregnancy test before administered study drug.
• Those who do not agree to use appropriate contraceptive methods (condom, diaphoretic, an intrauterine device, oral contraceptive hormones, or a vasectomy of male sex partner) during the clinical trials.
• Those who had experienced bleeding more 400ml or a blood donation within 8 weeks prior to the dosing of study drug.
• Those who had been abused alcohol or any other drug within 6 months.
• Those who are judged disqualified to join clinical trials by investigator for other clinically significant medical or psychiatric condition.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GC1102 80,000 IU(Single does); GC1102 80,000 IU(Single does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 120,000 IU(Single does); GC1102 120,000 IU(Single does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 180,000 IU(Single does); GC1102 180,000 IU(Single does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 240,000 IU(Single does); GC1102 240,000 IU(Single does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 80,000 IU(Multiple does); GC1102 80,000 IU(Multiple does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 120,000 IU(Multiple does); GC1102 120,000 IU(Multiple does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 180,000 IU(Multiple does); GC1102 180,000 IU(Multiple does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Experimental: GC1102 240,000 IU(Multiple does); GC1102 240,000 IU(Multiple does) I.V.	Biological: GC1102; GC1102(Recombinant Hepatitis B Human Immunoglobulin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicity after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks
Adverse events after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks
Clinical findings in physical examination, vital signs and clinical laboratory after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
HBsAg sero-conversion rate from positive to negative after the administration of GC1102 till End of Study visit	Part A: 4weeks, Part B: 7 weeks
Geometric mean titer of serum HBsAg at each measurement point after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks
Geometric mean titer of serum HBV DNA of each measurement point after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks
Occurrence rate of anti-GC1102 antibody	Part A: 4weeks, Part B: 7 weeks
Occurrence rate of HBV DNA sequence changes after the administration of GC1102	Part A: 4weeks, Part B: 7 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Ctrough for Part B	7 weeks
Terminal elimination half-life (t½β)	Part A: 4weeks, Part B: 7 weeks
Area under the time concentration curve from 0 to last and infinity (AUClast, AUC0-∞)	Part A: 4weeks, Part B: 7 weeks
Maximum plasma concentration(Cmax)	Part A: 4weeks, Part B: 7 weeks
Time to maximum plasma concentration (Tmax)	Part A: 4weeks, Part B: 7 weeks

Collaborators and Investigators

• Sponsor: Green Cross Corporation
• Investigators: Principal Investigator: Sang-Hoon An, M.D., Severance Hospital; Study Director: Chin Kim, Green Cross Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2015
• Primary Completion (Actual): October 12, 2017
• Study Completion (Actual): October 12, 2017

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): October 16, 2017
• Last Update Submitted That Met QC Criteria: October 13, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• 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; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: GC1102B_P1