A Study to Evaluate the Efficacy and Safety of Therapeutic Hepatitis B Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the evaluate and safety of the investigational medicinal product CVI-HBV-002.

Detailed Description
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A randomized, double-blinded, placebo-controlled, parallel, multicenter, phase 2b study to evaluate the efficacy and safety of CVI-HBV-002 in patients with chronic hepatitis B taking Tenofovir disoproxil fumarate/Tenofovir disoproxil

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Parallel, Multicenter, Phase 2b Study to Evaluate the Efficacy and Safety of CVI-HBV-002 in Patients With Chronic Hepatitis B Taking Tenofovir

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Biological: CVI-HBV-002
* Biological: Normal Saline(placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult between 19 to 60 years of age Those who have been diagnosed as chronic hepatitis B patients (e.g.HBsAg positive detected for 6 months or more) Started treatment with Tenofovir Disoproxil Fumarate(TDF) or Tenofovir Diproxil(TD), oral HBV antiviral agent, for 6 months to 5 years. HBsAg ≥ 100 IU/mL, HBV DNA ≤ 100 IU/mL at screening HBV DNA ≤ 2000 IU/mL at screening ALT ≤ Upper Limit of Normal) x 2 at screening Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Exclusion Criteria: Patients with other hepatic disease other than chronic hepatitis B(e.g., hemochromatosis, Wilson disease, alcoholic liver disease, nonalcoholic steatohepatitis, alpha-1 antitrypsin deficiency, etc) If any of the following laboratory tests were found at screening Total bilirubin > Upper Limit of Normal x 2 Prothrombin time delayed more than 3 seconds than normal Serum Albumin < 30 g/L (3 g/dL) Hemoglobin < 9.0 g/dL eGFR < 60 mL/min (Cockcroft-Gault) Absolute neutrophil count (ANC) < 1.5 x 10^9 /L (1500 /mm3) Platelet count < 100 x 10^9 /L (100 x 10^3 /mm3) Serum creatinine > 1.5 mg/dL Serum amylase > 2 x ULN and Lipase > 2 x ULN A history of ascites, jaundice, varicoses vein bleeding, hepatic encephalopathy, or other signs of liver failure Treated with oral antiviral agents or interferon therapy other than TDF(or TD) In case of receiving nephroxic drugs(Aminoglycosides, Amphotericin B, NSAIDs, etc.) within 14 days prior to screening When hepatotoxic drugs(Erythromycin, Ketoconazole, Rifampin, Fluconazole, Dapsone, etc.) are administered within 14 days prior to screening Patients with active bacterial, viral or fungal infections requiring systemic treatment Patients diagnosed with Alpha-fetoprotein (AFP) >50 ng/mL or with Hepatocellular Carcinoma (HCC) in screening Of those who have received immunosuppressive drugs within 6 months prior to screening, patients suspected of having decreased immunity by the judgment of the Investigator Patients who have received high dose (prednisone 20mg or more*) systemic corticosteroids for a long period of time(consecutive 14 days or longer) within 3 months before screening (at the discretion of the investigator in case of local corticosteroids) * Corresponding to 125 mg of cortisone, 100 mg of hydrocortisone, 20 mg of prednisone, 16 mg of methylpreprednisolone, 16 mg of triamsynolone, 3 mg of dexamethasone and 2.4 mg of betametasone. Patients who have been diagnosed with malignant tumors within 5 years before screening, or who have recurred malignant tumors(in case of benign tumors, if the Investigator considers that the progress of the clinical trial is not affected during the clinical trial) Organ transplantation recipients Patients with serious illnesses, such as heart failure, renal failure, and pancreatitis, other than liver disease Patients with a history of serious heart disease (NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring treatment or unstable angina) Patients with seizure disorders who require anticonvulsant therapy HbA1c>7.5% SBP≥140mmHg or DBP≥90mmHg Patients infected with hepatitis C(HCV), hepatitis D(HDV) or human immunodeficiency virus(HIV) A hypersensitivity or anaphylactic reaction to the components of the clinical trial drug or HBV vaccine components Continued drinking(>21 units/week, 1 unit = 10g of pure alcohol) or alcohol dependence Pregnancy or breastfeeding, or cannot agree with the approved method of contraception of the patient and partner during the clinical trial(e.g., infertility surgery, intrauterine contraceptive, oral contraceptive and concomitant use of diaphragm or condom, other hormonal delivery systems and concomitant use of diaphragm or condom) Patients who are concerned about the deterioration of daily function due to mental illness or who cannot understand the purpose and method of this trial Patient who has potential to severe febrile or systemic reaction Patients who are scheduled to participate in other clinical trials after enrolling in this trial, or have participated in other clinical trials within 3 month of enrollment in this trial Others those who are considered to be difficult to perform the clinical trial by the judgment of the Investigator

Ages Eligible for Study
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Minimum Age: 19 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVI-HBV-002<br>CVI-HBV-002 1.0mL(20ug/dose) Intramuscular injection at Baseline, Week 2, 4, 8, 12, 16, 20 / total 7 doses | Biological: CVI-HBV-002<br>* Investigational Product<br>|
| Placebo Comparator: Normal Saline<br>Normal Saline Choonwae Inj. 1.0 mL Intramuscular injection at Baseline, Week 2, 4, 8, 12, 16, 20 / total 7 doses | Biological: Normal Saline(placebo)<br>* Investigational Product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Mean Change in HBsAg(log10 IU/mL) | To evaluate mean changes in serum HBsAg(log 10 IU/mL) for patients treated with CVI-HBV-002 or Placebo at Week 48 versus Baseline | at week 48 from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Mean changes in serum HBsAg(log 10 IU/mL) | To evaluate mean changes in serum HBsAg(log 10 IU/mL) for patients treated with CVI-HBV-002 or Placebo at Week 24 versus Baseline | at week 24 from baseline | 
| Proportion assessment of Participants With HBsAg loss | To evaluate proportion of subjects with HBsAg loss for patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 | at weeks 24 and 48 | 
| Proportion assessment of Participants With HBsAg seroconversion | To evaluate proportion of subjects with HBsAg seroconversion for patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 | at weeks 24 and 48 | 
| Proportion assessment of Participants With HBeAg loss | To evaluate proportion of subjects with HBeAg loss for HBeAg positive patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 | at Weeks 24 and 48 | 
| Proportion assessment of Participants With HBeAg seroconversion | To evaluate proportion of subjects with HBeAg seroconversion for HBeAg positive patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 | at weeks 24 and 48 | 
| Evaluation of changes in HBV specific T cell immunity | Immune Response Rate of HBV specific T cell at Weeks 12 and 24 versus Baseline | at weeks 12 and 24 from baseline | 
| Proportion assessment of Participants With Virologic breakthrough | Proportion of subjects with experiencing virologic breakthrough | Baseline to week 48 | 
| Incidence assessment of Treatment-Emergent Adverse Evnent | Safety and tolerability assessment through incidence of Treatment-Emergent Adverse Evnent after treatment of Investigational Product | Baseline to Week 48 |