Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose
Primary Purpose
Encephalitis, Japanese
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Encephalitis, Japanese focused on measuring Japanese Encephalitis Vaccines, Flavivirus Infections
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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
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
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.
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.
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.
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
Full Information
NCT ID
NCT02514746
First Posted
July 15, 2015
Last Updated
September 24, 2020
Sponsor
PATH
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
1. Study Identification
Unique Protocol Identification Number
NCT02514746
Brief Title
Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
July 30, 2015 (Actual)
Primary Completion Date
December 15, 2016 (Actual)
Study Completion Date
January 12, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Encephalitis, Japanese
Keywords
Japanese Encephalitis Vaccines, Flavivirus Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
561 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine
Other Intervention Name(s)
CD-JEV, CD.JEVAX®, RS.JEV®
Intervention Description
0.5 mL subcutaneous injection
Primary Outcome Measure Information:
Title
Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV
Description
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.
Time Frame
3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)
Title
Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV
Description
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.
Time Frame
3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)
Secondary Outcome Measure Information:
Title
Seroprotection Rate 7 Days and 28 Days After Booster Dose
Description
Seroprotection rate is defined as the percentage of study participants with an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50.
Time Frame
7 days and 28 days following booster vaccination (Study Days 372 and 393)
Title
GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose
Description
Geometric mean titer of anti-JE neutralizing antibodies measured using PRNT-50.
Time Frame
7 days and 28 days following booster vaccination (Study Days 372 and 393)
Title
Seroconversion Rate 7 Days and 28 Days After Booster Dose
Description
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
Time Frame
7 days and 28 days following booster vaccination (Study Days 372 and 393)
Title
GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination
Description
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
Time Frame
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)
Title
Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination
Description
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.
Time Frame
30 minutes following booster vaccination (Study Day 365)
Title
Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination
Description
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.
Time Frame
From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)
Title
Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination
Description
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.
Time Frame
From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)
Title
Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination
Description
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
Time Frame
28 days following booster vaccination (Study Days 365 to 393)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
43 Months
Maximum Age & Unit of Time
51 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K Zaman, PhD, MPH, MBBS
Organizational Affiliation
International Centre for Diarrhoeal Disease Research, Bangladesh
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
25239483
Citation
Zaman K, Naser AM, Power M, Yaich M, Zhang L, Ginsburg AS, Luby SP, Rahman M, Hills S, Bhardwaj M, Flores J. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product. Vaccine. 2014 Oct 21;32(46):6061-6. doi: 10.1016/j.vaccine.2014.09.012. Epub 2014 Sep 18.
Results Reference
result
PubMed Identifier
35243320
Citation
Zaman K, Yunus M, Aziz AB, Feser J, Mooney J, Tang Y, Ellison DW, Thaisomboonsuk B, Zhang L, Neuzil KM, Marfin AA, Letson GW. Antibody persistence and immune memory response following primary vaccination and boosting with live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) in Bangladesh: A phase 4 open-label clinical trial. Vaccine X. 2022 Feb 5;10:100143. doi: 10.1016/j.jvacx.2022.100143. eCollection 2022 Apr.
Results Reference
derived
Learn more about this trial
Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose
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