Chronic Hepatitis B
Conditions
Keywords
Therapeutic vaccine, HBsAg clearance, Immune clearance, HBsAg clearance induced by vaccination, s seroconversion in carriers after vaccination
Brief summary
Background: The HBsAg clearance rate in interferon-treated responders is significantly higher than that in lamivudine-treated responders, implying immune control is the key to HBsAg clearance. There is a good chance to further increase the cure rate if the investigators can enhance the HBV-specific immune response when the HBsAg level already comes to a low level. Hypothesis: HBsAg-based vaccine can enhance HBsAg clearance in chronic hepatitis B patients whose HBsAg already \<=2000 IU/ml. Patients and methods: This pilot study will enroll 20 chronic hepatitis B patients with HBsAg ≦2000 IU/ml, no hepatic decompensation, no HIV coinfection, nor clinical immunodeficiency. Engerix-B vaccine (20μg for \<20 years old and 40 μg for ≥ 20 years old) will be given every 2 months for one year. HBsAg quantification, anti-HBs, and HBV DNA will be surveyed regularly before each dose during the treatment period and every 3 months for another year following the last dose. Viral and cellular factors will be studied to discover determinants affecting HBsAg clearance. Aims 1. To elucidate whether HBsAg-based vaccine can reactivate host immunity to eliminate chronic HBV infection in patients with low titer HBsAg. 2. To delineate the doses to response (HBsAg clearance or decline rate) correlation so as to design a feasible schedule for future clinical trials in a larger group of patients. 3. To discover viral and host factors which can be used as biomarkers for personalized vaccine therapy.
Detailed description
Vaccination schedule: Engerix-B (20μg/ml, GlaxoSmithKline Biologicals) will be administered intramuscularly at 0, 2, 4, 6, 8, 10, 12 months or until HBsAg clearance. The dosage will be 20μg in those \<= 20 years old and 40μg in those \> 20 years old. HBsAg and anti-HBs: qHBsAg will be checked by commercial kits (Elecsys, Roche Diagnostics, Indianapolis, IN) at baseline, right before every dose, and every 3 months following the last dose for one year. ALT, AST, Alpha-fetoprotein, bilirubin and anti-HBs will be checked simultaneously.
Interventions
BIOLOGICALHBV vaccine (Engerix B)
Engerix-B (20μg/ml, GlaxoSmithKline Biologicals) is administered intramuscularly at 0, 2, 4, 6, 8, 10, 12 months. The dosage will be 20μg in those \<= 20 years old and 40μg in those \> 20 years old.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Naïve or treated chronic hepatitis B patients with positive HBsAg and negative HBeAg; 2. Quantitative serum HBsAg (qHBsAg) \<2000 IU/ml; 3. No HIV co-infection; 4. No obvious immunodeficiency (such as renal failure, chemotherapy, radiotherapy, immunosuppressant); 5. Aged 3 to 80 years;
Exclusion criteria
1. Pregnancy 2. Allergic to HBV vaccine or yeast. 3. Hepatic decompensation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HBsAg Levels From Baseline to 2 Years | 2 years | The difference of HBsAg levels at the end of follow up (2 years) and baseline |
Secondary
| Measure | Time frame |
|---|---|
| Anti-HBs Seropositivity | 2 years |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engerix-B Engerix-B (20 μg/ml, GlaxoSmithKline) was administered at 0-2-4-6-8-10-12 months in dosage of 40μg for \>20 years old and 20μg for \< or =20 years old
HBV vaccine (Engerix B): Engerix-B (20μg/ml, GlaxoSmithKline Biologicals) is administered intramuscularly at 0, 2, 4, 6, 8, 10, 12 months. The dosage will be 20μg in those \<= 20 years old and 40μg in those \> 20 years old. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Engerix-B |
|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12.1 |
| Region of Enrollment Taiwan | 20 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Change in HBsAg Levels From Baseline to 2 Years
The difference of HBsAg levels at the end of follow up (2 years) and baseline
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engerix-B | Change in HBsAg Levels From Baseline to 2 Years | -0.27 log IU/ml | Standard Deviation 0.48 |
p-value: <0.05t-test, 2 sided
Secondary
Anti-HBs Seropositivity
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engerix-B | Anti-HBs Seropositivity | 2 Participants |