Clinical trial NCT04289987: A Study to Evaluate the Efficacy and Safety of Therapeutic Hepatitis B Vaccine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: CHA Vaccine Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-28
Enrollment: 134
Sex: ALL
Minimum age (years): 19
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of Mean Change in HBsAg(log10 IU/mL)
timeFrame: at week 48 from baseline
Secondary outcomes:
measure: Evaluation of Mean changes in serum HBsAg(log 10 IU/mL)
timeFrame: at week 24 from baseline
measure: Proportion assessment of Participants With HBsAg loss
timeFrame: at weeks 24 and 48
measure: Proportion assessment of Participants With HBsAg seroconversion
timeFrame: at weeks 24 and 48
measure: Proportion assessment of Participants With HBeAg loss
timeFrame: at Weeks 24 and 48
measure: Proportion assessment of Participants With HBeAg seroconversion
timeFrame: at weeks 24 and 48
measure: Evaluation of changes in HBV specific T cell immunity
timeFrame: at weeks 12 and 24 from baseline
measure: Proportion assessment of Participants With Virologic breakthrough
timeFrame: Baseline to week 48
measure: Incidence assessment of Treatment-Emergent Adverse Evnent
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Chung-ang University Hospital
state: Dongjak-gu
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St. Mary's Hospital
state: Eunpyeong-gu
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Guro-gu
city: Seongnam-si
country: Korea, Republic of
facility: CHA University Bundang Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Sedaemun-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
city: Seoul
country: Korea, Republic of
facility: Soon Chung Hyang University Hospital Seoul
state: Yongsan-gu
Study officials:
affiliation: Samsung Medical Center
name: Joon Hyeok Lee
role: PRINCIPAL_INVESTIGATOR
References: