Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose

Study Overview
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Brief Summary
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This study aims to understand the persistence of the Japanese encephalitis (JE) antibody response in previously vaccinated children. The proposed study will enrol Bangladeshi children who had previously participated in a lot to lot consistency study (JEV05; NCT01567865) of JE live attenuated SA 14-14-2 vaccine (CD-JEV).

Detailed Description
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Study participants previously immunized with CD-JEV (Clinical Trials identifier: NCT01567865, JEV05) will have serum collected three and four years after initial vaccination to assess long-term immunogenicity. Four years after receiving the initial dose of CD-JEV, eligible participants will be vaccinated with a second subcutaneous dose of CD-JEV to assess the antibody response. Participants will be monitored for safety for 28 days following receipt of the booster dose.

Official Title
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Assessment of Long Term Immunogenicity of Japanese Encephalitis Live Attenuated SA-14-14-2 Vaccine in Previously Vaccinated Bangladeshi Children and Antibody Response and Safety to a Booster Dose

Conditions
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Encephalitis, Japanese

Intervention / Treatment
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* Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant in JEV05 study (NCT01567865) and received one dose of CD-JEV. Resides in the Matlab or Mirpur study area. At least one parent or guardian willing to provide written informed consent. Exclusion Criteria: Received a second dose of Japanese encephalitis vaccine within the past three years. Received immunoglobulins and/or any blood products within 90 days prior to enrollment. Been diagnosed with a primary or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection within the past three years.

Ages Eligible for Study
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Minimum Age: 43 Months
Maximum Age: 51 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV)<br>Participants previously vaccinated with CD-JEV will receive a booster dose of live, attenuated Japanese encephalitis SA-14-14-2 vaccine four years after initial vaccination. | Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine<br>* 0.5 mL subcutaneous injection<br>* Other names: RS.JEV®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Seroprotection rate is defined as the percentage of participants with an anti-Japanese encephalitis (JE) neutralizing antibody titer ≥ 1:10 as measured using a 50% plaque reduction neutralization test (PRNT-50). Seroprotection was assessed at 3 and 4 years after the initial vaccination in Study JEV05, prior to participants receiving a booster vaccination in the current study. | 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365) | 
| Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | The geometric mean titer (GMT) of anti-JE neutralizing antibodies 3 and 4 years after initial vaccination with CD-JEV in Study JEV05 and prior to receiving the booster vaccination in the current study, measured using PRNT-50. | 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection Rate 7 Days and 28 Days After Booster Dose | Seroprotection rate is defined as the percentage of study participants with an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50. | 7 days and 28 days following booster vaccination (Study Days 372 and 393) | 
| GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | Geometric mean titer of anti-JE neutralizing antibodies measured using PRNT-50. | 7 days and 28 days following booster vaccination (Study Days 372 and 393) | 
| Seroconversion Rate 7 Days and 28 Days After Booster Dose | Seroconversion rate is defined as the percentage of study participants with either: For participants who were seronegative at Baseline (defined as anti-JE neutralizing antibody titer of < 1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): A change in serostatus from seronegative (anti-JE neutralizing antibody titer of < 1:10) to positive (anti-JE neutralizing antibody titer ≥ 1:10) For participants who were seropositive at Baseline (defined as an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): a 4-fold increase in anti-JE neutralizing antibody titer relative to Baseline anti-JE neutralizing antibody titer | 7 days and 28 days following booster vaccination (Study Days 372 and 393) | 
| GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | To evaluate the magnitude of the increase in GMTs, the GMT ratio of anti-JE neutralizing antibody titers between post-booster vaccination and pre-booster vaccination was calculated for the following: GMT of anti-JE neutralizing antibodies at 7 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies GMT of anti-JE neutralizing antibodies at 28 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies | 4 years after the initial vaccination (Study Day 365, pre-booster vaccination) and 7 and 28 days following booster vaccination (Study Days 372 and 393) | 
| Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | The number of participants with at least one occurrence of an immediate reaction, including local, systemic, or unsolicited adverse event that occurred within 30 minutes of the booster vaccination. | 30 minutes following booster vaccination (Study Day 365) | 
| Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Participants were monitored for local reactions from 30 minutes through 7 days post booster vaccination. Local reactions (at the injection site) included the following: Ecchymosis (bruising) Erythema (redness) Edema (swelling) Induration (hardness) Pain/tenderness Local ecchymosis, erythema, edema, and induration were graded as follows: Grade 1: ≤ 2.5 cm in diameter Grade 2: > 2.5 cm in diameter with < 50% surface area of extremity involved Grade 3: ≥ 50% surface area of extremity involved OR ulceration OR secondary infection OR phlebitis OR sterile abscess OR drainage Grade 4: potentially life-threatening consequences Injection site pain/tenderness were graded as follows: Grade 1: causing no or minimal limitation in use of limb Grade 2: causing greater than minimal limitation of use of limb Grade 3: causing inability to perform usual social or functional activities Grade 4: inability to perform basic self-care OR hospitalization indicated. | From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372) | 
| Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Participants were monitored for systemic reactions from 30 minutes through 7 days post booster vaccination. Systemic reactions (general signs / symptoms) included the following: Fever Change in eating habits Diarrhea Sleepiness Irritability Unusual crying Vomiting Fever was graded as follows: Grade 1: 37.5 ℃ to 37.9 ℃ Grade 2: 38.0 ℃ to 38.4 ℃ Grade 3: 38.5 ℃ to 40.0 ℃ Grade 4: > 40.0 ℃ Change in eating habits, diarrhea, sleepiness, irritability, unusual crying, vomiting were graded as follows: Grade 1: causing no or minimal interference with usual social or functional activities Grade 2: causing greater than minimal interference with usual social or functional activities Grade 3: causing inability to perform usual social or functional activities OR hospitalization indicated Grade 4: inability to perform basic self-care OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. | From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372) | 
| Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | AEs were graded for severity according to the following: Grade 1 (Mild): Symptoms causing no or minimal interference with usual social and functional activities Grade 2 (Moderate): Symptoms causing greater than minimal interference with usual social and functional activities Grade 3 (Severe): Symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated Grade 4 (Potentially life-threatening): Symptoms causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Relationship to study vaccine was based on the Clinician's assessment. A serious adverse event is defined as an AE that meets 1 of the following criteria: Death Life-threatening Requires hospitalization or prolongation of existing hospitalization Results in persistent disability Important medical event based on medical judgement | 28 days following booster vaccination (Study Days 365 to 393) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese Encephalitis Vaccines, Flavivirus Infections