Hepatitis B, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of the investigational medicinal product CVI-HBV-002.
Detailed description
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
Interventions
BIOLOGICALCVI-HBV-002
Investigational Product
BIOLOGICALNormal Saline(placebo)
Investigational Product
Sponsors
CHA Vaccine Institute Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Adult between 19 to 60 years of age 2. Those who have been diagnosed as chronic hepatitis B patients (e.g.HBsAg positive detected for 6 months or more) 3. Started treatment with Tenofovir Disoproxil Fumarate(TDF) or Tenofovir Diproxil(TD), oral HBV antiviral agent, for 6 months to 5 years. 4. HBsAg ≥ 100 IU/mL, HBV DNA ≤ 100 IU/mL at screening 5. HBV DNA ≤ 2000 IU/mL at screening 6. ALT ≤ Upper Limit of Normal) x 2 at screening 7. Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
Exclusion criteria
1. 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) 2. 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 3. A history of ascites, jaundice, varicoses vein bleeding, hepatic encephalopathy, or other signs of liver failure 4. Treated with oral antiviral agents or interferon therapy other than TDF(or TD) 5. In case of receiving nephroxic drugs(Aminoglycosides, Amphotericin B, NSAIDs, etc.) within 14 days prior to screening 6. When hepatotoxic drugs(Erythromycin, Ketoconazole, Rifampin, Fluconazole, Dapsone, etc.) are administered within 14 days prior to screening 7. Patients with active bacterial, viral or fungal infections requiring systemic treatment 8. Patients diagnosed with Alpha-fetoprotein (AFP) \>50 ng/mL or with Hepatocellular Carcinoma (HCC) in screening 9. 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 10. 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. 11. 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) 12. Organ transplantation recipients 13. Patients with serious illnesses, such as heart failure, renal failure, and pancreatitis, other than liver disease 14. 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) 15. Patients with seizure disorders who require anticonvulsant therapy 16. HbA1c\>7.5% 17. SBP≥140mmHg or DBP≥90mmHg 18. Patients infected with hepatitis C(HCV), hepatitis D(HDV) or human immunodeficiency virus(HIV) 19. A hypersensitivity or anaphylactic reaction to the components of the clinical trial drug or HBV vaccine components 20. Continued drinking(\>21 units/week, 1 unit = 10g of pure alcohol) or alcohol dependence 21. 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) 22. 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 23. Patient who has potential to severe febrile or systemic reaction 24. 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 25. Others those who are considered to be difficult to perform the clinical trial by the judgment of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Mean Change in HBsAg(log10 IU/mL) | at week 48 from baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion assessment of Participants With HBsAg loss | at weeks 24 and 48 | To evaluate proportion of subjects with HBsAg loss for patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 |
| Proportion assessment of Participants With HBsAg seroconversion | at weeks 24 and 48 | To evaluate proportion of subjects with HBsAg seroconversion for patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 |
| Proportion assessment of Participants With HBeAg loss | at Weeks 24 and 48 | To evaluate proportion of subjects with HBeAg loss for HBeAg positive patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 |
| Evaluation of Mean changes in serum HBsAg(log 10 IU/mL) | at week 24 from baseline | 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 |
| Evaluation of changes in HBV specific T cell immunity | at weeks 12 and 24 from baseline | Immune Response Rate of HBV specific T cell at Weeks 12 and 24 versus Baseline |
| Proportion assessment of Participants With Virologic breakthrough | Baseline to week 48 | Proportion of subjects with experiencing virologic breakthrough |
| Incidence assessment of Treatment-Emergent Adverse Evnent | Baseline to Week 48 | Safety and tolerability assessment through incidence of Treatment-Emergent Adverse Evnent after treatment of Investigational Product |
| Proportion assessment of Participants With HBeAg seroconversion | at weeks 24 and 48 | To evaluate proportion of subjects with HBeAg seroconversion for HBeAg positive patients treated with CVI-HBV-002 or Placebo at Weeks 24 and 48 |
Countries
South Korea
Outcome results
None listed