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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JEVAC | Experimental | JEVAC 0.5 mL/ dose subcutaneously injected on upper thigh at D0, 1-4wk, and 1 year |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JEVAC | Biological | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 28 days after second dose of JEVAC |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 28 days after second vaccination, before and 28 days after booster vaccination with JEVAC |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pornthep Chanthavanich, MD | Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department Tropical Pediatrics | Ratchathewi | Bangkok | 10400 | Thailand |
There was no subject who did not get the study vaccine after informed consent was signed.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | percentage of seroconversion | 28 days after second dose of JEVAC |
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In addition to systematic assessment on Day 0-14 after each vaccination, Any unsolicited AE was accessed within 28 days after each vaccination. Any SAE was accessed through the study period (1 yr +28 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Pornthep Chanthavanich | Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Thailand | 6623549161 | tmpct@mahidol.ac.th |
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| ID | Term |
|---|---|
| D004672 | Encephalitis, Japanese |
| ID | Term |
|---|---|
| D004671 | Encephalitis, Arbovirus |
| D018792 | Encephalitis, Viral |
| D020805 | Central Nervous System Viral Diseases |
| D002494 | Central Nervous System Infections |
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| Adverse Events of Vaccine |
To determine the adverse events of JEVAC |
| 7, 14, 28 days after each vaccination and throughout the study period for local, solicited systemic, unsolicited systemic and serious adverse events, respectively |
| Neutralizing Antibody Persistence One Year After the Primary Vaccination | To determine the neutralizing antibody persistence one year after the primary JEVAC vaccination. | 1 year after primary vaccination |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
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| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | titer | 28 days after second vaccination, before and 28 days after booster vaccination with JEVAC |
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| Secondary | Adverse Events of Vaccine | To determine the adverse events of JEVAC | Determined AEs by number of injections 152 injection for the first dose 151 injection for the second dose 145 injection for the third dose | Posted | Number | events | 7, 14, 28 days after each vaccination and throughout the study period for local, solicited systemic, unsolicited systemic and serious adverse events, respectively | injections | Participants |
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| Secondary | Neutralizing Antibody Persistence One Year After the Primary Vaccination | To determine the neutralizing antibody persistence one year after the primary JEVAC vaccination. | The analysis was excluded 5 subjects who had NT titer >10 on D0 | Posted | Number | participants | 1 year after primary vaccination |
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|
| 21 |
| 152 |
| 89 |
| 152 |
| bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| skin infection | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
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| seizure | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| infection (other) | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
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| pharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| skin infection | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| urticaria | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
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| contact dermatitis | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Fever | Infections and infestations | MedDRA (10.0) | Systematic Assessment | Axillary temperature greater than or equal 37.5 celsius |
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| chills | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| poor appetite | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| D007239 | Infections |
| D000069544 | Infectious Encephalitis |
| D001102 | Arbovirus Infections |
| D000079426 | Vector Borne Diseases |
| D000096724 | Mosquito-Borne Diseases |
| D014777 | Virus Diseases |
| D012327 | RNA Virus Infections |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D004660 | Encephalitis |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
| injections |
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