Safety and Efficacy Study of ChimeriVax™-JE and JE Inactivated Mouse Brain Vaccine in Children of Descending Age

Study Overview
=================
Brief Summary
-----------------
This randomised, double-blind study is to be conducted on 96 subjects at multiple sites in India. Subjects will be enrolled by age group and randomised to either ChimeriVax™-JE (JE-CV) or JE Mouse Brain Derived Vaccine (JE-MBDV). Study consists of a screening period, a treatment period and a 2 year follow-up period. Primary safety endpoints will be the adverse event (AE) rates 28 days after completion of vaccination course. The primary efficacy endpoints will be the rate of seroconversion 28 days after completing vaccination.

Official Title
-----------------
Randomised, Double Blind, Controlled, Safety, Tolerability and Immunogenicity Phase II Trial of ChimeriVax™-JE and Japanese Encephalitis Inactivated Mouse Brain Vaccine in Children of Descending Age.

Conditions
-----------------
Japanese Encephalitis

Intervention / Treatment
-----------------
* Biological: ChimeriVax™-JE
* Biological: Japanese Encephalitis Inactivated Mouse Brain Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All aspects of the Protocol explained and written informed consent obtained from the subject's parent or guardian and assent from the child if ≥ 8 years of age. Aged ≥ 9 months to < 10 years In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results Subject had to be available for the study duration for the study duration, including all planned follow-up visits. Exclusion Criteria: A history of vaccination against, or infection with, JE or other flaviviruses (e.g. Kyanasur Forest Disease, West Nile virus, dengue fever). Previous JE vaccination was to be determined by history (interview of subject's parent or guardian) or by inspecting the child's official vaccination record. Demonstration of parasitemia on malaria blood smear at Screening. History of residence in or travel to a JE-endemic region of India or elsewhere in Asia (for periods of 4 weeks or more). hypersensitivity to thimerosal or gelatin Have received a transfusion of blood, blood products or serum globulin in the preceding 6 months, Have an immunodeficiency or neurological disorder, or take drugs that suppress the immune system, Have a history of severe reaction to other vaccines, Have a chronic condition requiring medication, Intend to travel out of the area during the study period, Have spent at least 4 weeks in a JE-endemic region, Plan to receive any other vaccination within the double-blind treatment period, or who have received a vaccination in the month preceding Screening, Exhibit signs of secondary or tertiary malnutrition, Are seropositive to human immunodeficiency virus (HIV), Hepatitis B or C, Have malaria infection, or who have a fever within 3 days before vaccination. Those with an acute fever, or with previously scheduled vaccinations, may be rescheduled. Consideration of the routine immunisation schedule should be made such that it is ensured that routine vaccinations due are either given before entry to the trial, or afterwards if delayed because of the trial.

Ages Eligible for Study
-----------------
Minimum Age: 9 Months
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JE-CV Group<br>Participants will receive Japanese encephalitis chimeric virus vaccine (JE-CV) | Biological: ChimeriVax™-JE<br>* One dose of 4.0 log10 PFU is given in a volume of 1 ml for children aged > 3 years and 0.5 ml to children and infants aged < 3 years administered subcutaneously<br>|
| Active Comparator: MBDV Group<br>Participants will receive the mouse brain-derived vaccine (MBDV) | Biological: Japanese Encephalitis Inactivated Mouse Brain Vaccine<br>* Two doses of 1 ml reconstituted JE-MBDV is given to subjects aged > 3 years and 0.5 ml is given to children and infants aged < 3 years administered subcutaneously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events Following Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine |  | Day 14 up to Day 42 Post-vaccination | 
| Number of Participants With Treatment-Related Adverse Events Following Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine |  | Day 14 up to Day 42 Post-vaccination | 
| Number of Participants With Seroconversion After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine | Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). Seroconversion was defined as a titer ≥10 1/dil for participants who were seronegative at baseline and ≥ 4 fold rise for participants who were seropositive at baseline (titer ≥ 10 1/dil). | Day 42 Post-vaccination | 
| Geometric Mean Titers (GMTs) of Japanese Encephalitis Viruses After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine | Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). | Day 42 Post Dose 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroconversion After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine | Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). Seroconversion was defined as a titer ≥10 1/dil for participants who were seronegative at baseline and ≥ 4 fold rise for participants who were seropositive at baseline (titer ≥ 10 1/dil). | Day 42 Post Dose 1 | 
| Geometric Mean Titers (GMTs) Using Neutralizing Antibody to Japanese Encephalitis Viruses After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine | Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). | Day 42 Post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Japanese Encephalitis