Study of Japanese Encephalitis Chimeric Virus Vaccine Given With Measles-Mumps-Rubella Vaccine in Taiwanese Toddlers

Study Overview
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Brief Summary
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This study is designed to compare the immunogenicity of Japanese encephalitis chimeric virus vaccine (JE-CV) and measles-mumps-rubella (MMR)vaccine when given together or when given at separate visits 6 weeks apart in toddlers aged 12 to 18 months. Primary objective: To demonstrate the non-inferiority of the antibody responses in terms of seroconversion of the concomitant administration of JE-CV and MMR compared to the antibody responses after the single administration of JE-CV and MMR vaccine. Secondary objectives: To describe the immune response to JE CV and MMR before and after one dose of JE CV and MMR vaccine, respectively. To describe the safety of a single dose of JE-CV and MMR vaccine (given separately at a 6-week interval and the safety of the concomitant administration of JE-CV and MMR vaccine in all subjects up to 6 months after last vaccination.

Detailed Description
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All participants will receive Japanese encephalitis chimeric virus vaccine and measles-mumps-rubella vaccine and will be monitored for safety throughout the study.

Official Title
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Immunogenicity and Safety of Japanese Encephalitis Chimeric Virus Vaccine (JE CV) Concomitantly Administered With Measles, Mumps, and Rubella (MMR) Vaccine in Toddlers in Taiwan.

Conditions
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Measles, Japanese Encephalitis, Mumps, Rubella

Intervention / Treatment
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* Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus
* Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus
* Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Aged 12 to 18 months on the day of inclusion . Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg. Subject in good health based on medical history and physical examination. Provision of informed consent form signed by at least one parent or other legally acceptable representative, and by an independent witness if the parents or legally acceptable representative cannot read. Subject and parent/legally acceptable representative or delegate able to attend all scheduled visits and comply with all trial procedures. 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. Planned participation in another clinical trial during the present trial period. Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for pandemic influenza vaccination, which may be received at least two weeks before the study vaccines. Planned receipt of any vaccine up to the 6 weeks following the last trial vaccination except for pandemic influenza vaccine. In the event of a local or national immunization program with a pandemic influenza vaccine, participants who receive a pandemic influenza vaccine at any time during the trial will not be withdrawn from the trial. Previous vaccination against measles, measles-mumps-rubella (MMR), or flavivirus disease, including Japanese encephalitis (JE). Receipt of blood in the past 6 months that might interfere with the assessment of the immune response Receipt of intravenous injection of plasma, platelet product, or high dose of intravenous immunoglobulin in the past 11 months Receipt of intramuscular treatment of immunoglobulin or Hepatitis B immunoglobulin in the past 3 months 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 history of human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C seropositivity. History of measles, mumps, rubella, or flavivirus infection confirmed either clinically, serologically, or microbiologically. 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 . Known systemic hypersensitivity to gelatin, eggs, or anaphylactic/anaphylactoid reaction to neomycin. Known history of thrombocytopenia. Administration of any anti-viral within 2 months preceding first vaccination and up to the 6 weeks following the last trial vaccination. History of central nervous system disorder or disease, including seizures and febrile seizures. Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Participants will receive the Japanese encephalitis chimeric virus vaccine (JE-CV) on Day 0 and Measles, mumps, and rubella live attenuated virus vaccine (MMR) on Day 42 | Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus<br>* 0.5 mL each; Subcutaneous (SC)<br>* Other names: MMR II®;|
| Experimental: Group 2<br>Participants will receive Measles, mumps, and rubella live attenuated virus vaccine (MMR) on Day 0, and the Japanese encephalitis chimeric virus vaccine (JE-CV) on Day 42. | Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus<br>* 0.5 mL each, Subcutaneous (SC)<br>* Other names: MMR II®;|
| Experimental: Group 3<br>Participants will receive the Measles, mumps, and rubella live attenuated virus vaccine (MMR) and the Japanese encephalitis chimeric virus vaccine (JE-CV) on Day 0 | Biological: Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus<br>* 0.5 mL each, subcutaneous (SC)<br>* Other names: MMR II®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion to Vaccine Antigens Following Concomitant Administration of Japanese Encephalitis Chimeric Virus Vaccine (JECV) and MMR or Single Administration of JE-CV and MMR Vaccine at 42 Days Following First Vaccination | JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroconversion was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 and post-vaccination titer ≥1/10, or a pre-vaccination titer ≥1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer ≥120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer ≥1/10 U/ml when pre-vaccination titer is <10 U/ml; and for Rubella, post-vaccination titer ≥1/10 U/ml when pre-vaccination titer is <10 U/ml. | Day 0 (pre-vaccination) and Day 42 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion to JE-CV and MMR Antigens Before and 42 Days Following Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine | JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroconversion was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 and post-vaccination titer ≥1/10, or a pre-vaccination titer ≥1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer ≥120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer ≥1/10 U/ml when pre-vaccination titer is <10 U/ml; and for Rubella, post-vaccination titer ≥1/10 U/ml when pre-vaccination titer is <10 U/m | Pre-vaccination and Day 42 post-vaccination | 
| Number of Participants With Seroprotection to JE-CV and MMR Antigens Before, at Month 6 After Last Vaccination and Month 12 After First Following Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine | JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroprotection was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 (1/dil) and post-vaccination titer ≥1/10, (1/dil) or a pre-vaccination titer ≥1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer ≥120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer ≥1/10 units/ml when pre-vaccination titer is <10 units/ml; and for Rubella, post-vaccination titer ≥1/10 IU/ml when pre-vaccination titer is <10 IU/m | Pre-vaccination and up to Month 12 post-vaccination | 
| Geometric Mean Titers of Antibodies to Vaccine Antigens Before and After Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine | JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). | Pre-vaccination and Day 42 post-vaccination | 
| Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Administration of JE-CV Vaccine | Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling - ≥5 cm. Grade 3 systemic reactions: Fever - >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; Appetite Lost - Refused ≥3 feeds/meals or refused most feeds/meals; Irritability - Inconsolable. | Day 0 up to Day14 post-vaccination | 
| Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Administration of MMR Vaccine | Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling - ≥5 cm. Grade 3 systemic reactions: Fever - >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; Appetite Lost - Refused ≥3 feeds/meals or refused most feeds/meals; 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, Japanese encephalitis chimeric virus vaccine, Measles, Mumps, Rubella