Phase I Study to Investigate the Safety and Efficacy of HBV DNA Vaccine

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of a novel mixed plasmid DNA (HB-110) combined with an antiviral agent (Adefovir) for the patients with chronic Hepatitis B infection.

Official Title
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A Single Center, Randomized, Open-label, Dose Escalating Phase I Study to Evaluate the Safety of Intramuscularly Administered DNA Vaccine (HB-110) Combined With Oral Antiviral (Adefovir) in Subjects With Chronic Hepatitis B Over a 48-week Period

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Genetic: a mixed plasmid DNA (HB-110)
* Drug: Adefovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis B infected patient documented with positive HBsAg for 3 months and more at screening Chronic hepatitis B infected patient with positive HBeAg at screening Patient who has not treated with interferon alpha, lamivudine or adefovir within 3 months before study entry HBV DNA more than 1x10^5 copies/mL through COBAS Amplicor HBV monitor assay or bDNA method at screening Patient with HBV DNA decrease more than 10-fold compared to the baseline after 8 weeks treatment with adefovir Patient with ALT value between ULN x 1.5 and ULN x 5 at screening Patient given a written consent voluntarily Exclusion Criteria: Have uncompensated liver disease Serum creatinine > ULN x 1.5 Are positive for Hepatitis C, hepatitis D or HIV infection (confirmed by ELISA assay) Had a previous liver or bone marrow transplant Are currently taking any immunosuppressant or any possible immune modulatory drugs Women who are pregnant or breastfeeding Woman or man who plans a birth for study duration Any experience of severe adverse drug reaction or any medical history of severe allergic disease Patient with any severe disease (for example, heart failure, renal failure, pancreatitis, diabetes mellitus) affecting the study in discretion of investigator except liver disease Patient with any other liver disease but hepatitis B (for example, hemochromatosis, Wilson's disease, alcoholic/non-alcoholic liver diseae) Patient with intrahepatic tumors confirmed by imaging (liver biopsy)and abnormally increased alpha-fetoprotein Patient with any present malignant tumor except liver or its history Other inappropriate patient in discretion of investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br>HB-110 2mg, 4mg or 8mg combined with Adefovir | Genetic: a mixed plasmid DNA (HB-110)<br>* HB-110 2mg (or 4mg or 8mg), im, every other week, from week 0 to week 22 (total 12 injections) and Adefovir(Adefovir dipivoxil 10mg), od, from week -10 to from week 48.<br>|
| Active Comparator: II<br>Adefovir | Drug: Adefovir<br>* Adefovir(Adefovir dipivoxil)10mg, od, from week -10 to week 48.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and clinical laboratory abnormalities |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg/HBsAg seroconversion rate, HBV Ag specific T cell immunity |  | 24, 28, 32, 42, 44, and 48 week |