Safety and Immunogenicity of JECEVAX in Young Children

Study Overview
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Brief Summary
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A dose escalating study with 3 different dosing regimens of the studied vaccine (JECEVAX- VABIOTECH-Vietnam) and a licensed vaccine (JEVAX-VABIOTECH-Vietnam) is conducted in Vietnamese children, aged 9 to 24 months to assess the safety and immunogenicity. Two hundred children are enrolled and randomly assigned into 4 groups (50 children/group), each of which receive 2 doses of study / control vaccine subcutaneously, at 10-12 days interval. Safety issues included immediate reaction at the site of injection and systemic reaction within 30 min of administration, solicited and unsolicited adverse events occurs from the first dose to 30 days after second dose; SAE (from start of first dose to 30 days after second dose), blood cell count, urea, ALT, AST. Immunogenicity outcomes include seroconversion of neutralizing antibodies (blood samples are taken prior to 1st dose and 20-22 days post 2nd dose).

Detailed Description
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Mouse brain-derived Japanese Encephalitis (JE) vaccine was developed in Vietnam since 1989 with the support from WHO and BIKEN institute, Japan. It helped Viet Nam prevents Japanese Encephalitis outbreaks successfully during those years. However, mouse brain-derived JE vaccine production requires companies to compliance various requirements from WHO. Especially, WHO has a plan to replace the mouse brain-derived JE vaccines with Cell culture-derived JE vaccines. Vero cell-derived vaccine technology shows many advantages compares to Mouse brain-derived vaccine technology. VABIOTECH has been approved and sponsored by the Ministry of Science and Technology to produce Vero cell - derived JE vaccine. The vaccine demonstrated a good safety and immunogenicity profile in animal models. The vaccine has been proven safety in volunteer adults. In this study, a dose escalating study with 3 different dosing regimens of the studied vaccine (JECEVAX) and a licensed vaccine (JEVAX-VABIOTECH Vietnam) is conducted in Vietnamese children, aged 9-24 months to assess the safety and immunogenicity. Two hundred children are enrolled and randomly assigned into 4 groups (50 children/group), each of which receive 2 doses of investigate vaccines or control vaccine subcutaneously, at 10-12 days interval. Safety issues included immediate reaction at the site of injection and systemic reaction within 30 min of administration, solicited and unsolicited adverse events occurs from the first dose to 30 days after second dose; SAE (from start of first dose to 30 days after second dose), blood cell count, urea, ALT, AST. Immunogenicity outcomes include seroconversion of neutralizing antibodies (blood samples are taken prior to 1st dose and 20-22 days post 2nd dose).

Official Title
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Safety and Immunogenicity of an Inactivated Japanese Encephalitis Vaccine (JECEVAX) in Vietnamese Children

Conditions
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Japanese Encephalitis

Intervention / Treatment
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* Biological: JEVAX
* Biological: JECEVAX-1
* Biological: JECEVAX-0.8
* Biological: JECEVAX-0.5


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children of both sexes, 9-24 months of age; Have not been vaccinated with JE vaccine; Not have any chronic disease; Parents/legal guardians agree to participate their children in this study and sign the informed consent. Exclusion Criteria: Currently has chronic diseases (cardiovascular, liver and spleen related etc); Currently has acute diseases; Use (orally or injection) with corticosteroid containing drug (>1 mg / kg dose); Use of immunocompromised treatment within 4 weeks of enrollment; Being immunocompromised and autoimmune diseases (HIV, lupus); The family history of immunocompromised; History of febrile seizure; Allergic to any vaccine component; Fever (>38 Celsius degree) within 3 days before vaccination or at enrollment; Malnourished (3rd grade or above); Blood disorder; Use of vaccines which have not been licenced 7 days before enrolment in this study

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JECEVAX-1<br>JECEVAX - VABIOTECH Vietnam Liquid form Composition: 1.0 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12days | Biological: JECEVAX-1<br>* JECEVAX - VABIOTECH Vietnam Liquid form Composition: 1 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days<br>* Other names: JECEVAX-HI;|
| Experimental: JECEVAX-0.8<br>JECEVAX - VABIOTECH Vietnam Liquid form Composition: 0.8 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days | Biological: JECEVAX-0.8<br>* JECEVAX - VABIOTECH Vietnam Liquid form Composition: 0.8 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days<br>* Other names: JECVAX-MED;|
| Experimental: JECEVAX-0.5<br>JECEVAX - VABIOTECH Vietnam Liquid form Composition: 0.5 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days | Biological: JECEVAX-0.5<br>* JECEVAX - VABIOTECH Vietnam Liquid form Composition: 0.5 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days<br>* Other names: JECEVAX-LOW;|
| Active Comparator: JEVAX<br>JEVAX - VABIOTECH Vietnam Liquid form Composition: 1,0 BR209 Subcutaneous injection 0.5ml/dose, 2 doses, interval 10-12 days | Biological: JEVAX<br>* JEVAX - VABIOTECH Vietnam Liquid form Subcutaneous injection 0.5ml/dose, 2 doses, 10-12 days interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events during study period. | Number of participants with solicited and unsolicited adverse events after each dose of vaccine: immediately injection site and systemic AEs after vaccination (within 30 min), solicited and unsolicited AEs within 7 days after each dose, unsolicited AEs from day 8 after dose 1 to date of dose 2 and from day 8 after dose 2 to day 30 post 2nd dose, as assessed by CTCAE v.4.0. | Up to 30 days after 2nd dose | 
| Number of participants have sero-conversion at 20-22 days post 2nd dose (compared to pre-vaccination) | Sero-conversion rate of each JECEVAX regimen and JEVAX at 20-22 days after 2 doses of vaccines | Up to 20-22 days after the 2nd dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related SAE during study period | Number of participants with treatment-related SAE during study period of JECEVAX compared to that of JEVAX, as assessed by CTCAE ver 4.0 | Up to 30 days after the 2nd dose | 
| Number of participants with abnormal laboratory value. | Numbers of participants with abnormal laboratory values (blood cell counts, urea concentration, liver function (ALT, AST concentration) when administered with different JECEVAX formulations and with JEVAX before the first dose and 20-22 days after the 2nd dose. | Up to 20-22 days after the 2nd dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese Encephalitis, JECEVAX, Vietnam