Determining Long-Term Safety and Efficacy of Japanese Encephalitis Vaccine When Given With Measles Vaccine

Study Overview
=================
Brief Summary
-----------------
The previously conducted JEV01 study looked at the immunogenicity and safety of the concurrent administration of Japanese Live Attenuated SA 14-14-2 and measles vaccines at the one month post vaccination time point. The purpose of the JEV01 study was to help ensure the safety of SA 14-14-2 simultaneously administered with measles vaccine, paving the way for its use in routine EPI programs. As a follow-on to JEV01, this study will enroll those infants who received both vaccines and completed the JEV01 study. This study, however, will provide crucial data to help ensure the long-term immunogenicity of the concurrent administration of these vaccines and provide valuable information to determine the use of these vaccines in routine immunization programs. This study is planned because in the original protocol for JEV01, long-term data points were not included. The hypothesis is that children who receive JE live attenuated SA 14-14-2 vaccine and measles vaccine at the same time have long-term (24 and 36 months post vaccination) protection against these diseases at the same level as those who receive the vaccines at different intervals.

Detailed Description
-----------------
Japanese encephalitis is the leading cause of viral neurological disease and disability in Asia. The severity of sequelae, together with the volume of cases, make JE the most important cause of viral encephalitis in the world. Approximately 3 billion people-including 700 million children-live in Asian areas at risk for JE. JE most commonly infects children between the ages of 1 and 15 years, and can also infect adults in areas where the virus is newly introduced. More than 50,000 cases are reported annually and cause an estimated 10,000 to 15,000 deaths. This figure is believed to represent only a small proportion of the disease burden that actually exists. An effective vaccine has existed since 1941, but has not reached the poorest countries in Asia. During the 60 years that the vaccine has been available, JE has infected an estimated 10.5 million children, resulting in more than 3 million deaths and more than 4 million children living with long-term disabilities. Control of this disease has been limited due to poor disease surveillance, a limited and unstable vaccine supply, lack of guidance and programmatic support for immunization, and limited advocacy. A successful vaccine should be safe, efficacious, affordable, administered in a single dose, and easily incorporated into the routine Expanded Programmes on Immunization (EPI) programs. This trial is designed to determine the potential interference between the measles vaccine and the Japanese encephalitis vaccine at 12, 24, and 36 months post-vaccination. As these vaccines will be used in routine EPI systems at the same time, similar to how measles and yellow fever vaccine (also a Flavivirus) are administered, it is imperative to collect long-term data showing that neither vaccine interferes with seroconversion of the other when co-administered.This information will help to ensure subject safety and facilitate programmatic efficiency, reducing the number of immunization visits for both parents and health care workers.

Official Title
-----------------
Long-Term Assessment at 24 Months Post-Vaccination of the Non-Inferiority of the Concurrent Administration of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine and Measles Vaccine to Measles Vaccine Given Alone

Conditions
-----------------
Encephalitis, Japanese B

Intervention / Treatment
-----------------
* Biological: Live attenuated SA 14-14-2 vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant was enrolled in the JEV01 study previously conducted at RITM. Participant completed his/her vaccination schedule for the JEV01 study previously conducted at RITM. Participant's blood test results from JEV01 study indicate that he/she had seroconverted to measles vaccination. Participant's parents or legal guardian are/is willing to provide signed informed consent. Exclusion Criteria: Participant was withdrawn from the JEV01 study for any reason. Receipt of immune globulin or other blood products within 6 months of study (JEV02) entry or receipt of injected or oral corticosteroids or other immune modulator therapy (except routine vaccines) within 4 weeks of study (JEV02) entry. Any condition that in the opinion of the investigator, would interfere with the evaluation of the study objectives.

Ages Eligible for Study
-----------------
Minimum Age: 20 Months
Maximum Age: 36 Months

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>JE live attenuated SA 14-14-2 vaccine then measles vaccine after one month | Biological: Live attenuated SA 14-14-2 vaccine<br>* Live attenuated SA 14-14-2 vaccine coadministered with live measles vaccine (experimental Group)<br>|
| Experimental: Group 2<br>JE live attenuated SA 14-14-2 vaccine and measles vaccine concurrently | Biological: Live attenuated SA 14-14-2 vaccine<br>* Live attenuated SA 14-14-2 vaccine coadministered with live measles vaccine (experimental Group)<br>|
| Other: Group 3<br>Measles vaccine then JE live attenuated SA 14-14-2 vaccine after one month | Biological: Live attenuated SA 14-14-2 vaccine<br>* Live attenuated SA 14-14-2 vaccine coadministered with live measles vaccine (experimental Group)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measles Seropositivity at 24 and 36 Months | Seropositivity defined as an anti-MV IgG concentration of 120 mIU/mL determined with the Siemens ELISA | 24, 36 months post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measles Seropositivity at 12 Months | Seropositivity defined as an anti-MV IgG concentration of 120 mIU/mL determined with the Siemens ELISA | 12 months post vaccination | 
| Seropositive Rate for Japanese Encephalitis (JE) Antibody in Infants in the Philippines Who Received Measles Vaccine (MV) Before, With, or After SA 14-14-2 JE Vaccination by Month After JE Vaccination. | Seropositive defined as a person with neutralizing antibody against JE virus at a titer ≥ 1:10 in a 50% plaque-reduction neutralizing assay (PRNT-50) | 12 months, 24 months, and 36 months post vaccination | 
| Geometric Mean Neutralizing Antibody Titer to Japanese Encephalitis (JE) Virus in Infants in the Philippines Who Received Measles Vaccine (MV) Before, With, or After SA 14-14-2 JE Vaccination by Month After JE Vaccination. | Neutralizing antibody titer determined using a 50% plaque-reduction neutralizing assay (PRNT-50) for JE virus | 12, 24, 36 months post-JE vaccination | 

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