A Study to Evaluate the Safety and Efficacy of Therapeutic Hepatitis B Vaccine
- Conditions
- Hepatitis B, Chronic
- Interventions
- Biological: CVI-HBV-002
- Registration Number
- NCT02693652
- Lead Sponsor
- CHA Vaccine Institute Co., Ltd.
- Brief Summary
A single center, open labeled phase I/IIa study to evaluate safety, tolerability and efficacy of a therapeutic hepatitis B vaccine in oral antiviral drug-treated chronic hepatitis B virus carriers
- Detailed Description
* Objectives: To explore the appropriate dose of a therapeutic hepatitis B vaccine through the evaluation of safety, tolerability, and efficacy
* Subjects: Chronic hepatitis B carrier with normal ALT range
* Study hypothesis: The immune tolerance break and strong immune responses in the chronic hepatitis B carrier could be achieved with therapeutic hepatitis B vaccine containing novel adjuvant
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- Adult between 19 to 60 years of age
- Chronic hepatitis B carriers (HBsAg positive over 6 months)
- HBeAg positive patient, or patient who had lost HBeAg during Antiviral drug treatment
- Antiviral drug treated patient reducing the HBV DNA level below 2000 IU/mL measured by COBAS TaqManM HBV Test (Duration of drug administration should be over 6 months and no limitation on the type of antiviral drug)
- Patient has low ALT than 1.1 fold of upper limit of normal ALT level at screening
- Patient is able to provide written informed consent by oneself or legal representative
-
Patient has liver diseases except chronic hepatitis B (i.e. hematochromatosis, alcoholic liver disease, nonalcoholic fatty liver disease, alpha-1 antitrypsin deficiency etc.)
-
Patient has one or more test results and symptoms at the screening
- ALT > upper limit of normal level X 1.1
- Total bilirubin > upper limit of normal
- Prothrombin time > Over 3 second than normal
- Serum Albumin < 30 g/L (3 g/dL)
- Patient has history of ascites, yellow jaundice, variceal hemorrhage, hepatic encephalopathy, or liver failure
- Liver FibroScan > F3 (F0: no fibrosis, F1: portal fibrosis, F2: periportal fibrosis, F3: septal fibrosis, F4: cirrhosis)
-
Patient has one or more test results at the screening
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count (ANC) < 1.5 x 109 /L (1500 /mm3)
- Platelet count < 100 x 109 /L (100 x 103 /mm3)
- Serum creatinine > 1.5 mg/dL
- Serum amylase > 2 x ULN and Lipase > 2 x ULN
-
Patient has history of Interferon treatment
-
Patient is pregnant or breastfeeding or intending to become pregnant during the study
-
Patient has active microbial, viral, or fungal infections in need of systemic treatment
-
Alpha-fetoprotein (AFP) > 50 ng/mL or Hepatocellular Carcinoma (HCC) patient
-
Among the patients treated with immunosuppressive drug within 6 months before screening, suspected case of the declined immunity in the opinion of the investigator
-
Patient had long term systemic treatment (more than 14 days consecutively) of high dose (over 20 mg of prednisolone or equivalent dose*) corticosteroid (Decision to participate of patient who had local treatment of corticosteroid is allowed in the opinion of the investigator)
*equivalent to cortisone 125 mg, hydrocortisone 100 mg, prednisone 20 mg, methylprednisolone 16 mg, triamcinolone 16 mg, dexamethasone 3 mg, or betamethasone 2.4 mg
-
Patient diagnosed with a malignant tumor within 5 years before screening or relapsed patient (Benign tumor patient is able to participate in this study at the discretion of the investigator)
-
Patient has history of organ transplantation
-
Patient has serious disease judged by investigator such as heart failure, renal failure, and pancreatitis
-
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
-
Uncontrollable diabetic patient (FBS>130mg/dl, HbA1c>7.5%)
-
Uncontrollable hypertension patient (SBP≥140mmHg 또는 DBP≥90mmHg)
-
HCV, HDV, or HIV patient
-
Patient has a plan to participate in other clinical study, or took part in other clinical study within 1 month before enrollment
-
Patient has hypersensitivity or anaphylactic reaction for components of investigational product or HBV vaccine
-
Patient has continuous drinking (>21 units/week, 1 unit = 10g of pure alcohol) or dependence on alcohol
-
Patient concerned about the decline in daily activity or not able to understand the objectives and methods due to the psychiatric problems
-
Patient has potential to severe febrile or systemic reaction
-
Subject unacceptable in this study under the opinion of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CVI-HBV-002 (20ug, 6 shots) CVI-HBV-002 * HBV surface antigen 20ug/dose * Intramuscular injection at 0, 1, 2, 3, 4, 5 month CVI-HBV-002 (40ug, 3 shots) CVI-HBV-002 * HBV surface antigen 40ug/dose * Intramuscular injection at 0, 1, 2 month CVI-HBV-002 (40ug, 6 shots) CVI-HBV-002 * HBV surface antigen 40ug/dose * Intramuscular injection at 0, 1, 2, 3, 4, 5 month CVI-HBV-002 (20ug, 3 shots) CVI-HBV-002 * HBV surface antigen 20ug/dose * Intramuscular injection at 0, 1, 2 month
- Primary Outcome Measures
Name Time Method Safety and tolerability (including incidence of adverse events or expected adverse reactions for vaccine treatment) measured for 7 days after each vaccination 7 days after each vaccination Occurrence of severe local and/or systemic tolerability signs and symptoms measured for 7 days after each vaccination
- Secondary Outcome Measures
Name Time Method HBeAg loss at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) HBeAg disappearance at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) comparing with that of baseline
HBe seroconversion rate at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) HBeAg seroconversion rate at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) comparing with that of baseline
HBsAg loss at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) HBsAg disappearance at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) comparing with that of baseline
HBsAg seroconversion rate at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) HBsAg seroconversion rate at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) comparing with that of baseline
HBV specific T cell immunity at the 3rd month (for 3 shot group) or 6th month (for 6 shot group) HBV specific T cell response at the 3rd month (for 3 shot group) or 6th month (for 6 shot group) comparing with that of baseline
HBV DNA level at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) HBV DNA level at the 3rd and 5th month (for 3 shot group) or 6th and 8th month (for 6 shot group) comparing with that of baseline
Trial Locations
- Locations (1)
Bundang CHA General Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of