Open-label, Randomized Study in a Pediatric Population in a JEV (Japanese Encephalitis Virus)-Endemic Country

Study Overview
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Brief Summary
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This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in study IC51-323.

Detailed Description
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This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in the previous study IC51-323.

Official Title
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Long-Term Immunity and Safety With or Without a Booster Dose Following Primary Vaccination With the Japanese Encephalitis Vaccine IC51 (IXIARO®) in a Pediatric Population in a JEV-Endemic Country. Open-Label, Randomized, Phase 3 Study

Conditions
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Japanese Encephalitis

Intervention / Treatment
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* Biological: IXIARO
* Biological: IXIARO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children and adolescents who have completed study IC51-323 and received both IXIARO vaccinations according to protocol. Children who have received the dose confirmed for their age group. Male or female healthy children and adolescents aged ≥9 months to <17 years and 7 months at the time of enrolment into this study. Written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable. Female subjects: either no childbearing potential or negative pregnancy test (pregnancy test to be performed in female subjects after onset of menarche) at Visits 1, 2 and 2a as stipulated by the protocol. For females after menarche willingness to practice a reliable method of contraception Exclusion Criteria: Vaccination against JE virus (JEV) (except within study IC51-323 and IC51 325), Yellow fever, West Nile virus and Dengue fever at any time prior to or planned during the study. History of or clinical manifestation of any Flavivirus disease during IC51-323 or IC51 325. Participation in another study with an investigational drug during IC51 323 or IC51 325. Planned active or passive immunization within 2 weeks before and 1 week after the IXIARO booster. History of or development of any immunodeficiency including post-organ-transplantation after inclusion into IC51-323 or IC51 325. History of or development of an autoimmune disease during study IC51-323 or IC51 325. Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying medications started during IC51-323 or IC51 325. (For corticosteroids, this would mean prednisone or equivalent at >0.05 mg/kg/day; topical and inhaled steroids are allowed). Acute febrile infection at Visit 2 (only for the Booster Group). Pregnancy (positive pregnancy test at Visit 1 and Visit 2), lactation or unreliable contraception in female subjects after onset of menarche. Hypersensitivity reactions to IXIARO or adverse events in study IC51-323 requiring withdrawal from further vaccination or anaphylaxis or severe cases of atopy requiring emergency treatment or hospital admission during IC51-323 or IC51 325. History of urticaria after hymenoptera envenomation, drugs, physical or other provocations or of idiopathic cause during IC51-323 or IC51 325. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) (measurement of Hepatitis B surface antigen [HBsAg] titers) or hepatitis C virus (HCV). Illicit drug use and/or current drug or alcohol addiction. Inability or unwillingness by the legal representative(s) and/or the subject (where applicable) to provide informed consent/assent and to abide by the requirements of the study. Persons who have been committed to an institution (by a court or by an authority).

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: >14 months to <2 years<br>IXIARO 0.25 ml i.m. (milliliter, intramuscular) | Biological: IXIARO<br>* 0.25 ml i.m. (milliliter, intramuscular)<br>|
| Active Comparator: >3 years - <18 years<br>IXIARO 0.5 ml i.m (milliliter, intramuscular) | Biological: IXIARO<br>* 0.5 ml i.m. (milliliter, intramuscular)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCRs (Seroconversion Rate) as Defined by Percentage of Subjects With Plaque Reduction Neutralization Test Titers of>1:10 at 1 Month After the Booster Dose |  | 1 month post booster | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Subjects Achieving a >4-fold Increase in JEV (Japanese Encephalitis Virus) Neutralizing Antibody Titers at 1 Month After the Booster Dose |  | 1 month | 
| GMTs (Geometric Mean Titre) for JEV Neutralizing Antibodies Measured Using a Validated PRNT (Plaque Reduction Neutralization Test) at 1 Month After the Booster Dose |  | 1 month | 
| GMTs and Rate of Subjects With a PRNT Titer of >1:10 at Months 12, 24 and 36 After First IXIARO Vaccination in IC51-323 With and Without Booster Vaccination |  | 36 months | 
| Rate of Subjects With SAEs (Serious Adverse Events) Following Immunization and Medically Attended AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and |  | 36 months | 
| Rate of Subjects With Unsolicited AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and Relationship to Vaccinations. |  | 36 months | 
| Rate of Subjects With SAEs and Medically Attended AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations. |  | 1 month | 
| Rate of Subjects With Unsolicited AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations. |  | 1 month | 
| Rate of Subjects With Solicited AEs for up to 7 Days Following the Booster Dose. Severity and Duration. |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune response, IC51-325, Japanese Encephalitis, Intercell AG