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

Phase 4

Completed

• Conditions: Encephalitis, Japanese
• Interventions: Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine

• Registration Number: NCT02514746
• Lead Sponsor: PATH

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-07-15
• Study Start: 2015-07-30
• Study First Submitted QC: 2015-07-30
• Study First Posted: 2015-08-04
• Primary Completion: 2016-12-15
• Study Completion: 2017-01-12
• Status Verified: 2020-08
• Results First Submitted: 2020-09-17
• Results First Submitted QC: 2020-09-24
• Last Update Submitted: 2020-09-24
• Results First Posted: 2020-10-19
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 561

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV)	Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine	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.

Primary Outcome Measures

Name	Time	Method
Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV	3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)	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.
Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV	3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)	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.

Secondary Outcome Measures

Name	Time	Method
GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose	7 days and 28 days following booster vaccination (Study Days 372 and 393)	Geometric mean titer of anti-JE neutralizing antibodies measured using PRNT-50.
Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination	From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)	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.
Seroprotection Rate 7 Days and 28 Days After Booster Dose	7 days and 28 days following booster vaccination (Study Days 372 and 393)	Seroprotection rate is defined as the percentage of study participants with an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50.
GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination	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)	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
Seroconversion Rate 7 Days and 28 Days After Booster Dose	7 days and 28 days following booster vaccination (Study Days 372 and 393)	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
Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination	From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)	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.
Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination	28 days following booster vaccination (Study Days 365 to 393)	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
Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination	30 minutes following booster vaccination (Study Day 365)	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.