A Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of the Third Generation Hepatitis B Vaccine

Study Overview
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Brief Summary
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A single center, randomized, double blinded phase I/IIa exploratory study to evaluate reactogenicity, safety, immunogenicity and dose-response of a new hepatitis B vaccine in human adult

Detailed Description
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Objectives: To explore the most effective dose of the third generation Hepatitis B vaccine through the evaluation of reactogenicity, safety, and immunogenicity. Subjects: Adults having anti-HBs antibody titers less than 10 mIU/mL after 3 previous injections of the conventional Hepatitis B vaccine. Study hypothesis: The third generation Hepatitis B vaccine, containing preS antigens in addition to S antigen, has an ability to elicit faster protection and higher antibody titers than the second generation Hepatitis B vaccine in the subjects.

Official Title
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A Single Center, Randomized, Double Blinded PhaseI/IIa Exploratory Study to Evaluate Reactogenicity, Safety, Immunogenicity and Dose Response of a New Hepatitis B Vaccine in Human Adult

Conditions
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Healthy

Intervention / Treatment
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* Biological: CVI-HBV-001
* Biological: Conventional Hepatitis B vaccine (20 μg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults between 20 and 50 years of age Anti-HBs titers < 10 mIU/mL Subject is able to provide written informed consent by oneself or legal representative Exclusion Criteria: Hepatitis B core antibodies positive patient Patient has abnormal results in liver-function test Patient has active microbial, viral, or fungal infections in need of systemic treatment Patient has history of serious heart disease (NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, treatment required ventricular tachyarrhythmias, or unstable angina etc.) Patient has seizure disorder required anticonvulsants treatment Serious chronic obstructive pulmonary disease patient accompanied hypoxemia Uncontrollable diabetic patient Uncontrollable hypertension patient Patient with known history of HIV, HBV, or HCV infection Subject had experience of participating other clinical study or clinical treatment within 30 days before screening Subject has hypersensitivity or anaphylactic reaction for HBV vaccine components Patient being treated for prolonged immunosuppressive therapy (including steroids) Hemodialysis patient Subject has continuous drinking (>21 units/week, 1 unit = 10g of pure alcohol) or dependence on alcohol Subject is pregnant or breastfeeding or intending to become pregnant during the study Subject has any other significant findings unacceptable in this study under the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVI-HBV-001 (5 μg)<br>HBV surface antigen 5 μg/dose Intramuscular injection at 0, 1, 6th month | Biological: CVI-HBV-001<br>* Investigational Product<br>|
| Experimental: CVI-HBV-001 (10 μg)<br>HBV surface antigen 10 μg/dose Intramuscular injection at 0, 1, 6th month | Biological: CVI-HBV-001<br>* Investigational Product<br>|
| Experimental: CVI-HBV-001 (20 μg)<br>HBV surface antigen 20 μg/dose Intramuscular injection at 0, 1, 6th month | Biological: CVI-HBV-001<br>* Investigational Product<br>|
| Experimental: CVI-HBV-001 (40 μg)<br>HBV surface antigen 40 μg/dose Intramuscular injection at 0, 1, 6th month | Biological: CVI-HBV-001<br>* Investigational Product<br>|
| Active Comparator: Conventional Hepatitis B vaccine (20 μg)<br>HBV surface antigen 20 μg/dose Intramuscular injection at 0, 1, 6th month | Biological: Conventional Hepatitis B vaccine (20 μg)<br>* Investigational Product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and reactogenicity (including incidence of adverse events and expected adverse reactions for vaccine treatment) measured for 7 days after each vaccination | Occurrence of severe local and/or systemic reactogenicity signs and symptoms measured for 7 days after each vaccination | 7 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rate | Seroprotection (> 10 mIU/mL of anti-HBs) rate measured 4 weeks after vaccination | 4 weeks after vaccination | 
| Antibody titers to HBsAg | Geometric mean titer (GMT, mIU/mL) measured 4 weeks after vaccination | 4 weeks after vaccination |