Encephalitis, Japanese B
Conditions
Keywords
inactivated Japanese encephalitis vaccine, vero cell, children, immunogenicity, safety
Brief summary
Japanese encephalitis (JE) is the main cause of viral encephalitis in many countries of Asia including Thailand. Estimated annual mortality ranges from10,000-15,000 deaths, while the total number of clinical cases is about 50,000. Of these cases, about 50% result in permanent neuropsychiatric sequelae. The disease occurs mostly among children aged \<10 years. There is no specific antiviral treatment for JE. Vaccination is the single most important control measure. This study aims to evaluate the immunogenicity and safety of inactivated Vero cell derived JE vaccine (Beijing P-3 strain) produced by Liaoning Cheng Da Biotechnology Co., Ltd, China JEVAC in Thai children. 152 healthy Thai children aged between 1-3 years will be vaccinated with JEVAC in a dose of 0.5 mL. subcutaneously on Day 0, 1-4 weeks later and a booster vaccination at one year (totally 3 doses). Two mL. of blood will be drawn on Day 0, 4 weeks after second dose, at one year on booster vaccination day and 4 weeks after the booster (totally 8 mL. of 13 months study period) for determination of JE neutralizing antibodies (PRNT50) using Beijing P3 strain. Adverse events will be observed for 28 days after each vaccination. Serious adverse events will be observed throughout the study period.
Interventions
BIOLOGICALJEVAC
Each subject will receive 3 doses of JEVAC subcutaneously on Day 0, 1-4 weeks and a booster vaccination at one year. Each dose of JEVAC contains 0.5 mL. of inactivated Vero cell derived JE vaccine (Beijing P-3 strain).
Sponsors
Mahidol University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 3 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy Thai children aged 1- 3 years 2. No previous history of JE vaccination 3. Available for all visited schedule in the study period. 4. Written inform consent signed by a parent or guardian
Exclusion criteria
1. Known serious underlying diseases such as nervous system, heart, kidney and liver diseases. 2. Known hypersensitivity to JE vaccine composition such as human albumin, dextran 40, etc. 3. Previous history of JE disease. 4. Receive the blood component within the past 3 months, 5. Known history of immunocompromised conditions such as HIV/AIDS, malignancy. 6. Under treatment of immunosuppressive drugs such as systemic corticosteroid and anti-neoplastic drug. 7. Febrile illness (temperature ≥37.5°C) or acute illness/infection on the day of vaccination 8. Plan to leave the study area before the end of study period. 9. Participating in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate After Primary Vaccination | 28 days after second dose of JEVAC | To determine the seroconversion rate by using neutralizing antibody (NT) against JE virus (Beijing P3 strain) JE virus from \<10 on before first vaccination To \>= 10 at 28 days after second vaccination (primary vaccination). Those who have NT titer \>=10 before first vaccination, will not be included in immunogenicity evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer of NT After Primary and Booster Vaccination | 28 days after second vaccination, before and 28 days after booster vaccination with JEVAC | To determine the geometric mean titers (GMT) of neutralizing antibody of JEVAC 1 month after primary and then before and after booster vaccinations. |
| Adverse Events of Vaccine | 7, 14, 28 days after each vaccination and throughout the study period for local, solicited systemic, unsolicited systemic and serious adverse events, respectively | To determine the adverse events of JEVAC |
| Neutralizing Antibody Persistence One Year After the Primary Vaccination | 1 year after primary vaccination | To determine the neutralizing antibody persistence one year after the primary JEVAC vaccination. |
Countries
Thailand
Participant flow
Recruitment details
The enrollment took place in 2 sites (Department of Tropical Pediatrics, Faculty of Tropical Medicine and Nopparat Rajathanee Hospital) from 3rd May 2010 to 10th August 2010. One hundred and fifty two subjects who illegible for the inclusion and exclusion criteria were enrolled in the study.
Pre-assignment details
There was no subject who did not get the study vaccine after informed consent was signed.
Participants by arm
| Arm | Count |
|---|---|
| JEVAC JEVAC : Each subject will receive 3 doses of JEVAC subcutaneously on Day 0, 1-4 weeks and a booster vaccination at one year. Each dose of JEVAC contains 0.5 mL. of inactivated Vero cell derived JE vaccine (Beijing P-3 strain). | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | JEVAC |
|---|---|
| Age, Categorical <=18 years | 152 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 1.2 years STANDARD_DEVIATION 0.32 |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 89 / 152 |
| serious Total, serious adverse events | 21 / 152 |
Outcome results
Primary
Seroconversion Rate After Primary Vaccination
To determine the seroconversion rate by using neutralizing antibody (NT) against JE virus (Beijing P3 strain) JE virus from \<10 on before first vaccination To \>= 10 at 28 days after second vaccination (primary vaccination). Those who have NT titer \>=10 before first vaccination, will not be included in immunogenicity evaluation.
Time frame: 28 days after second dose of JEVAC
Population: There were 152 enrolled subjects in the study. However, 5 subjects had NT titer \>= 10 before first vaccination and one subject whom blood on 28days after second vaccination was not drawn due to withdrawn consent. Therefore, the number of subjects for the outcome measurement should be 146.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JEVAC | Seroconversion Rate After Primary Vaccination | 100 percentage of seroconversion |
Secondary
Adverse Events of Vaccine
To determine the adverse events of JEVAC
Time frame: 7, 14, 28 days after each vaccination and throughout the study period for local, solicited systemic, unsolicited systemic and serious adverse events, respectively
Population: Determined AEs by number of injections 152 injection for the first dose 151 injection for the second dose 145 injection for the third dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JEVAC | Adverse Events of Vaccine | 79 events |
| GMT of NT Before Booster Vaccine | Adverse Events of Vaccine | 5 events |
| GMT of NT Titer After Booster Vaccine | Adverse Events of Vaccine | 3 events |
| Poor Appetite After Vaccination | Adverse Events of Vaccine | 24 events |
| Vomiting After Vaccination | Adverse Events of Vaccine | 36 events |
| Urticaria After Vaccination | Adverse Events of Vaccine | 3 events |
| Unsolicited AEs After Each Vaccination | Adverse Events of Vaccine | 63 events |
| SAEs Entire the Study | Adverse Events of Vaccine | 21 events |
Secondary
Geometric Mean Titer of NT After Primary and Booster Vaccination
To determine the geometric mean titers (GMT) of neutralizing antibody of JEVAC 1 month after primary and then before and after booster vaccinations.
Time frame: 28 days after second vaccination, before and 28 days after booster vaccination with JEVAC
Population: 152 were enrolled, 1 withdrawn consent before second vaccine, 5 had NT \>= 10 before first vaccine, 146 included in D28 after second vaccine. At 1 year, 3 received JE vaccine outside the study, 3 lost follow up, 140 included in before booster, At D28 after booster, 1 could not draw blood, 139 included in D28 after booster.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| JEVAC | Geometric Mean Titer of NT After Primary and Booster Vaccination | 150.01 titer |
| GMT of NT Before Booster Vaccine | Geometric Mean Titer of NT After Primary and Booster Vaccination | 49.33 titer |
| GMT of NT Titer After Booster Vaccine | Geometric Mean Titer of NT After Primary and Booster Vaccination | 621.66 titer |
Secondary
Neutralizing Antibody Persistence One Year After the Primary Vaccination
To determine the neutralizing antibody persistence one year after the primary JEVAC vaccination.
Time frame: 1 year after primary vaccination
Population: The analysis was excluded 5 subjects who had NT titer \>10 on D0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JEVAC | Neutralizing Antibody Persistence One Year After the Primary Vaccination | 125 participants |