Chronic Hepatitis B
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALGC1102
GC1102(Recombinant Hepatitis B Human Immunoglobulin)
Sponsors
Green Cross Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity 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 |
| Adverse events after the administration of GC1102 | Part A: 4weeks, Part B: 7 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Geometric mean titer of serum HBsAg at each measurement point after the administration of GC1102 | Part A: 4weeks, Part B: 7 weeks |
| 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 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
| Measure | Time frame |
|---|---|
| Area under the time concentration curve from 0 to last and infinity (AUClast, AUC0-∞) | Part A: 4weeks, Part B: 7 weeks |
| Time to maximum plasma concentration (Tmax) | Part A: 4weeks, Part B: 7 weeks |
| Terminal elimination half-life (t½β) | Part A: 4weeks, Part B: 7 weeks |
| Ctrough for Part B | 7 weeks |
| Maximum plasma concentration(Cmax) | Part A: 4weeks, Part B: 7 weeks |
Countries
South Korea
Outcome results
None listed