Immunogenicity and Safety of ChimeriVax™ Japanese Encephalitis Vaccine in Thai Toddlers and Children

Study Overview
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Brief Summary
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Safety: To describe the safety profiles following vaccination. Immunogenicity: To describe the immune response after a single dose of vaccine.

Detailed Description
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This is a randomized, cross-over, open, active controlled, multi-center trial in toddlers and children in Thailand. Stepwise enrollment of children in 2 age cohorts. Subjects will be followed for 5 years.

Official Title
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A Controlled Study of the Safety and Immunogenicity of ChimeriVax™ Japanese Encephalitis Vaccine in Thai Toddlers and Children

Conditions
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Japanese Encephalitis, Hepatitis A

Intervention / Treatment
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* Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)
* Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)
* Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)
* Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of consent form signed by at least one parent or another legally acceptable representative, and by at least one independent witness. Completion of vaccinations according to the national immunization schedule Subject and parent/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures. Previous receipt of two doses of a mouse-brain-derived JE vaccine at 12 to 15 months of age according to the national immunization schedule and aged 2 to 5 years on the day of inclusion. Aged 12 to 24 months on the day of inclusion and have not received any JE vaccine. Exclusion Criteria: Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination. 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 the trial vaccine or 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. Receipt of hepatitis A vaccine. History of flavivirus infection (confirmed either clinically, serologically or microbiologically). Administration of any anti-viral within 2 months preceding the screening visit. History of central nervous system disorder or disease. Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia. Planned participation in another clinical trial during the present trial period. 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, hepatitis B or hepatitis C seropositivity in the blood sample taken at screening. Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination. Previous vaccination against flavivirus disease at any time before the trial other than a mouse-brain-derived JE vaccine given in a two-dose regimen at 12 to 15 months of age in accordance with the national immunization schedule. Febrile illness or any acute illness/infection on the day of vaccination, according to investigator judgment History of seizures. Previous vaccination against flavivirus disease.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 5 Years

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JE-CV/Hepatitis A (Group 1)<br>Participants aged 2 to 5 years at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28) | Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)<br>* ≥4.0 Log10 Plaque forming units (PFU), Subcutaneous (SC; Day 0); 0.5 mL intramuscular (IM; Day 28)<br>* Other names: ChimeriVax™-JE;|
| Experimental: Hepatitis A/JE-CV (Group 2)<br>Participants aged 2 to 5 years at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28) | Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)<br>* 0.5 mL IM (Day 0); ≥4.0 Log10 PFU SC (Day 28)<br>* Other names: ChimeriVax™-JE;|
| Experimental: JE-CV/Hepatitis A (Group 3)<br>Participants aged 12 to 24 months at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28) | Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)<br>* ≥4.0 Log10 PFU SC (Day 0); 0.5 mL IM (Day 28)<br>* Other names: ChimeriVax™-JE;|
| Experimental: Hepatitis A/JE-CV (Group 4)<br>Participants aged 12 to 24 months at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28) | Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)<br>* 0.5 mL IM (Day 0); ≥4.0 Log10 PFU SC (Day 28)<br>* Other names: ChimeriVax™-JE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as First Injection | 12 to 24 months - Injection site: Tenderness, Erythema, and Swelling; Systemic reactions: Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥5 cm; Fever, >39.5˚C; Vomiting, ≥ 6 times/day; Abnormal crying, >3 hours; Drowsiness, Sleeping often; Appetite lost, Refuses ≥3 feeds/meals; Irritability, Inconsolable. 2 to 5 years - Injection site: Pain, Erythema, and Swelling; Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating; Erythema and Swelling, ≥5 cm; Fever, >39˚C; Headache, Malaise, and Myalgia, Prevents activities. | Day 0 up to Day 14 post-vaccination | 
| Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as Second Injection | 12 to 24 months - Injection site: Tenderness, Erythema, and Swelling; Systemic reactions: Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥5 cm; Fever, >39.5˚C; Vomiting, ≥ 6 times/day; Abnormal crying, >3 hours; Drowsiness, Sleeping often; Appetite lost, Refuses ≥3 feeds/meals; Irritability, Inconsolable. 2 to 5 years - Injection site: Pain, Erythema, and Swelling; Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating; Erythema and Swelling, ≥5 cm; Fever, >39˚C; Headache, Malaise, and Myalgia, Prevents activities. | Day 0 up to Day 14 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion to JE-CV Vaccine Antigens Following Administration of JE-CV Vaccination | JE virus neutralizing antibody measurement was assessed by 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 after final vaccination | 
| Summary of Geometric Mean Titers Against JE Antibodies Before and After JE-CV Vaccination | JE virus neutralizing antibody measurement was assessed by the PRNT50 assay. | Day 0 (pre-vaccination) and Day 28 after final vaccination | 

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