Study of ChimeriVax™-Japanese Encephalitis Vaccine in Toddlers in Thailand and the Philippines

Study Overview
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Brief Summary
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This study is to assess the safety and immunogenicity of three consecutive lots of JE-CV in toddlers aged 12-18 months. Primary objective: To demonstrate the bio-equivalence of three lots of JE-CV vaccine manufactured by sanofi pasteur. Secondary objective: To describe the safety of vaccination in all subjects

Detailed Description
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This is a Phase III trial in toddlers in Thailand and the Philippines.

Official Title
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Lot-to-lot Consistency, Bridging, and Safety Trial of ChimeriVax™-Japanese Encephalitis Vaccine in Toddlers in Thailand and the Philippines

Conditions
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Japanese Encephalitis, Hepatitis A

Intervention / Treatment
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* Biological: Japanese encephalitis vaccine
* Biological: Japanese encephalitis vaccine
* Biological: Japanese encephalitis vaccine
* Biological: Japanese encephalitis vaccine (Acambis)
* Biological: Hepatitis A vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Aged 12 to 18 months on the day of inclusion. In good general health, without significant medical history. Provision of informed consent form signed by at least one parent or other legally acceptable representative, and by at least one independent witness if required by local regulations. Subject and parent/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures. Completion of vaccinations according to the national immunization schedule. Exclusion Criteria : Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the trial vaccination. Planned participation in another clinical trial during the present trial period. Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy. Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing any of the same substances. Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator. Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of the immune response. Administration of any anti-viral within 2 months preceding V01. History of central nervous system disorder or disease, including seizures. Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia. Receipt of any vaccine in the 4 weeks preceding the first trial vaccination. Planned receipt of any vaccine in the 4 weeks following any trial vaccination. Personal human immunodeficiency virus seropositivity in the blood sample taken at screening. Receipt of any JE vaccine or hepatitis A vaccine. Previous vaccination against flavivirus disease. History of flavivirus infection (confirmed either clinically, serologically or microbiologically) Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular vaccination. Febrile illness (temperature ≥38°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JE-CV GPO MBP (Lot 1)<br>Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 1. | Biological: Japanese encephalitis vaccine<br>* 0.5 mL, Subcutaneous<br>* Other names: ChimeriVax™-JE;|
| Experimental: JE-CV GPO MBP (Lot 2)<br>Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 2. | Biological: Japanese encephalitis vaccine<br>* 0.5 mL, Subcutaneous<br>* Other names: ChimeriVax™-JE;|
| Experimental: JE-CV GPO MBP (Lot 3)<br>Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 3. | Biological: Japanese encephalitis vaccine<br>* 0.5 mL, Subcutaneous<br>* Other names: ChimeriVax™-JE;|
| Active Comparator: JE-CV WRAIR (Group 4)<br>Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) | Biological: Japanese encephalitis vaccine (Acambis)<br>* 0.5 mL, Subcutaneous<br>|
| Sham Comparator: Hepatitis A (Group 5)<br>Participants 12 to 18 months of age randomized to receive Hepatitis A vaccine | Biological: Hepatitis A vaccine<br>* 0.5 mL, Intramuscular<br>* Other names: Avaxim® 80U Pediatric;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroconversion to Vaccine Antigens Following Vaccination With JE-CV by GPO MBP Lots | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as participants with a pre-vaccination titer <10 1/dil and post-vaccination titer ≥ 10 1/dil, or participants with pre-vaccination titer ≥ 10 1/dil and 4-fold increase from pre- to post-vaccination. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers Against the Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or Walter Reed Army Institute of Research (WRAIR) JE-CV | Anti-Japanese Encephalitis Chimeric Virus antibodies were measured using the 50% plaque reduction neutralization test (PRNT50) assay. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants With Seroprotection to Japanese Encephalitis Chimeric Virus Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or WRAIR JE-CV | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the PRNT50 assay. Seroprotection was defined as the proportion of subjects with a JE CV virus PRNT50 neutralizing antibody titer ≥10 1/dilution (dil). | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Titers Ratios Against the Japanese Encephalitis Chimeric Virus (JE-CV) Antigen Following Vaccination With One of the JE-CV by GPO MBP Lots or WRAIR JE-CV Vaccine | Anti Japanese encephalitis chimeric virus antibodies were measured using the PRNT50 assay. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With a Japanese Encephalitis Chimeric Virus Vaccine (JE- CV) by GPO MBP Lot or WRAIR JE-CV, or Hepatitis A Vaccine. | Solicited injection site: Tenderness, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Tenderness, cries when injected limb is moved or the movement of injected limb is reduced; Erythema and Swelling ≥5 cm. Grade 3 systemic reactions: Fever, temperature >39.5˚C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal, >3 hours; Drowsiness, sleeping most of the time or difficult to wake up; Appetite Lost, refuses ≥3 or most feeds/meals; and Irritability, inconsolable. | Day 0 up to Day 14 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese encephalitis, Hepatitis A, Inactivated Mouse-Brain