Encephalitis, Japanese
Conditions
Keywords
Japanese Encephalitis Vaccines, Flavivirus Infections
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.
Interventions
BIOLOGICALLive Attenuated Japanese Encephalitis SA-14-14-2 Vaccine
0.5 mL subcutaneous injection
Sponsors
International Centre for Diarrhoeal Disease Research, Bangladesh
PATH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
43 Months to 51 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
Participant flow
Recruitment details
This study enrolled Bangladeshi children who had participated in Study JEV05 (NCT01567865) and received a single dose of live attenuated Japanese encephalitis vaccine (CD-JEV). The first visit in this study was 3 years after vaccination in JEV05. At the 2nd study visit, 4 years after initial vaccination, children received a booster dose of CD-JEV.
Pre-assignment details
Children were analyzed based on whether they received vaccine from the new or old facility in Study JEV05: * Group A: Received CD-JEV from new facility in Study JEV05 * Group B: Received CD-JEV from old facility in Study JEV05
Participants by arm
| Arm | Count |
|---|---|
| Group A: CD-JEV Participants previously vaccinated with CD-JEV manufactured in the new facility received a booster dose of live, attenuated Japanese encephalitis SA-14-14-2 vaccine by subcutaneous injection four years after initial vaccination. | 437 |
| Group B: CD-JEV Participants previously vaccinated with CD-JEV manufactured in the old facility received a booster dose of live, attenuated Japanese encephalitis SA-14-14-2 vaccine by subcutaneous injection four years after initial vaccination. | 124 |
| Total | 561 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Chronically Ill | 1 | 2 |
| Overall Study | Other | 5 | 1 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 10 |
Baseline characteristics
| Characteristic | Group B: CD-JEV | Total | Group A: CD-JEV |
|---|---|---|---|
| Age, Continuous | 47.8 months STANDARD_DEVIATION 1.4 | 47.7 months STANDARD_DEVIATION 1.6 | 47.7 months STANDARD_DEVIATION 1.6 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Bangladesh | 124 Participants | 561 Participants | 437 Participants |
| Sex: Female, Male Female | 65 Participants | 291 Participants | 226 Participants |
| Sex: Female, Male Male | 59 Participants | 270 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 424 | 0 / 109 | 0 / 533 |
| other Total, other adverse events | 57 / 424 | 26 / 109 | 83 / 533 |
| serious Total, serious adverse events | 0 / 424 | 0 / 109 | 0 / 533 |
Outcome results
Primary
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.
Time frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)
Population: Enrolled participants with at least one serology result at Year 3 (Day 1) or Year 4 (Day 365), prior to receiving the booster dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group A: CD-JEV | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 5.8 titer |
| Group A: CD-JEV | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 6.1 titer |
| Group B: CD-JEV | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 5.8 titer |
| Group B: CD-JEV | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 6.0 titer |
| Total | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 5.8 titer |
| Total | Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 6.1 titer |
Comparison: Geometric mean titer ratio at Year 395% CI: [0.9, 1.1]
Comparison: Geometric mean titer ratio at Year 495% CI: [0.9, 1.1]
Primary
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.
Time frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)
Population: Enrolled participants with at least one serology result at Year 3 (Day 1) or Year 4 (Day 365), prior to receiving the booster dose (long-term assessment intention-to-treat population \[ITT\]).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: CD-JEV | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 9.2 percentage of participants |
| Group A: CD-JEV | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 12.5 percentage of participants |
| Group B: CD-JEV | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 9.8 percentage of participants |
| Group B: CD-JEV | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 11.9 percentage of participants |
| Total | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 3 | 9.3 percentage of participants |
| Total | Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV | Year 4 | 12.4 percentage of participants |
Comparison: Difference at Year 395% CI: [-7.5, 4.5]
Comparison: Difference at Year 495% CI: [-7.4, 6.5]
Secondary
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.
Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)
Population: Participants who received the booster dose of CD-JEV and had at least one serology result 7 days or 28 days after the booster vaccination (ITT booster analysis set).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group A: CD-JEV | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 7 days after booster | 98.8 titer |
| Group A: CD-JEV | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 28 days after booster | 156.2 titer |
| Group B: CD-JEV | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 7 days after booster | 135.4 titer |
| Group B: CD-JEV | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 28 days after booster | 215.4 titer |
| Total | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 7 days after booster | 105.4 titer |
| Total | GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose | 28 days after booster | 167.0 titer |
Comparison: Geometric mean titer ratio 7 days after booster dose95% CI: [0.5, 1]
Comparison: Geometric mean titer ratio 28 days after booster dose95% CI: [0.6, 0.9]
Secondary
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
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)
Population: Participants who received the booster dose of CD-JEV and had at least one serology result 7 days or 28 days after the booster vaccination (ITT booster analysis set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: CD-JEV | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 7 days after booster | 16.2 ratio |
| Group A: CD-JEV | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 28 days after booster | 25.9 ratio |
| Group B: CD-JEV | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 7 days after booster | 22.5 ratio |
| Group B: CD-JEV | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 28 days after booster | 35.9 ratio |
| Total | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 7 days after booster | 17.3 ratio |
| Total | GMT Ratio of Anti-JE Neutralizing Antibody Titers Between Post-Booster and Pre-Booster Vaccination | 28 days after booster | 27.7 ratio |
Secondary
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.
Time frame: 30 minutes following booster vaccination (Study Day 365)
Population: Participants who received the booster vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site pain | 1 Participants |
| Group A: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Any immediate reaction | 3 Participants |
| Group A: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site swelling | 3 Participants |
| Group B: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site pain | 0 Participants |
| Group B: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Any immediate reaction | 1 Participants |
| Group B: CD-JEV | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site swelling | 1 Participants |
| Total | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Any immediate reaction | 4 Participants |
| Total | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site swelling | 4 Participants |
| Total | Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination | Injection site pain | 1 Participants |
Secondary
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.
Time frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)
Population: Participants who received the booster vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Edema | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Any Local Reaction | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Induration | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness - Grade 1 | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Erythema | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Ecchymosis | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Any Local Reaction | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Ecchymosis | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Erythema | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Edema | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Induration | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness - Grade 1 | 1 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Erythema | 0 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness - Grade 1 | 2 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Pain/tenderness | 2 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Ecchymosis | 0 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Edema | 0 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Any Local Reaction | 2 Participants |
| Total | Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination | Induration | 0 Participants |
Secondary
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.
Time frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)
Population: Participants who received the booster vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting | 2 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits - Grade 1 | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 1 | 8 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Sleepiness | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Diarrhea | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Any systemic reaction | 14 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever | 10 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Unusual crying | 0 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 2 | 4 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting - Grade 1 | 2 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability - Grade 1 | 1 Participants |
| Group A: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Diarrhea | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Any systemic reaction | 5 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever | 3 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 1 | 3 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 2 | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits - Grade 1 | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Sleepiness | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability - Grade 1 | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Unusual crying | 0 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting | 1 Participants |
| Group B: CD-JEV | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting - Grade 1 | 1 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability | 1 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 2 | 4 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting | 3 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Irritability - Grade 1 | 1 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever - Grade 1 | 11 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Any systemic reaction | 19 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Unusual crying | 0 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Diarrhea | 0 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits - Grade 1 | 2 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Fever | 13 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Sleepiness | 0 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Change in eating habits | 2 Participants |
| Total | Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination | Vomiting - Grade 1 | 3 Participants |
Secondary
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
Time frame: 28 days following booster vaccination (Study Days 365 to 393)
Population: Participants who received the booster vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Any adverse events | 57 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Mild adverse events | 48 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Moderate adverse events | 8 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Severe adverse events | 1 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Life-threatening adverse events | 0 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Related adverse events | 3 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Unrelated adverse events | 54 Participants |
| Group A: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Serious adverse events | 0 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Moderate adverse events | 4 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Unrelated adverse events | 25 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Severe adverse events | 0 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Life-threatening adverse events | 0 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Related adverse events | 1 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Any adverse events | 26 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Mild adverse events | 22 Participants |
| Group B: CD-JEV | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Serious adverse events | 0 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Moderate adverse events | 12 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Mild adverse events | 70 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Any adverse events | 83 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Severe adverse events | 1 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Unrelated adverse events | 79 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Related adverse events | 4 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Life-threatening adverse events | 0 Participants |
| Total | Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination | Serious adverse events | 0 Participants |
Secondary
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
Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)
Population: Participants who received the booster dose of CD-JEV and had at least one serology result 7 days or 28 days after the booster vaccination (ITT booster analysis set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: CD-JEV | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 88.7 percentage of participants |
| Group A: CD-JEV | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 96.4 percentage of participants |
| Group B: CD-JEV | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 91.6 percentage of participants |
| Group B: CD-JEV | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 98.2 percentage of participants |
| Total | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 89.3 percentage of participants |
| Total | Seroconversion Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 96.8 percentage of participants |
Comparison: Difference at 7 days post booster vaccination95% CI: [-8, 4.5]
Comparison: Difference at 28 days post booster vaccination95% CI: [-4.4, 3]
Secondary
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.
Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)
Population: Participants who received the booster dose of CD-JEV and had at least one serology result 7 days or 28 days after the booster vaccination (ITT booster analysis set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: CD-JEV | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 90.6 percentage of participants |
| Group A: CD-JEV | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 97.8 percentage of participants |
| Group B: CD-JEV | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 94.4 percentage of participants |
| Group B: CD-JEV | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 99.1 percentage of participants |
| Total | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 7 days after booster | 91.4 percentage of participants |
| Total | Seroprotection Rate 7 Days and 28 Days After Booster Dose | 28 days after booster | 98.1 percentage of participants |
Comparison: Difference at 7 days post booster vaccination95% CI: [-8.1, 2.8]
Comparison: Difference at 28 days post booster vaccination95% CI: [-3.3, 3]