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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: GC1102


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |