Encephalitis, JapanesePhase 4NCT02514746
Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose
A Phase 4 study testing Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine in people with Encephalitis, Japanese, run by PATH.
Trial 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… Read more about this study
- Who is it for?
- Ages 43 to 51 monthsHealthy volunteers can take part
- Conditions the study is for
- Encephalitis, Japanese
- What is being tested?
- Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 561 participants
- Where
- No sites listed yet
- Study dates
- 30 Jul 2015to 12 Jan 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 43 to 51 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
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
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).
Read the 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.
- Conditions
- Encephalitis, Japanese
- Being tested
- Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine
- Keywords
- Japanese Encephalitis Vaccines, Flavivirus Infections
- Medical subject headings
- Encephalitis, Japanese, Flavivirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live Attenuated Japanese Encephalitis SA-14-14-2 VaccineBiological
Also called CD-JEV, CD.JEVAX®, RS.JEV®
0.5 mL subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV) | Experimental | 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. Receives: Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 28 days following booster vaccination (Study Days 365 to 393)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2015 (estimated)
- Study start30 Jul 2015
- Primary completion15 Dec 2016
- Study completion12 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Encephalitis, JapaneseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 561 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Responsible party
- Sponsor
- Investigators
- K Zaman, PhD, MPH, MBBS, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02514746
- Sponsor's protocol ID
- JEV07
- Other IDs
- PR-15036
- Status last verified
- Aug 2020
- First submitted
- 15 Jul 2015
- Last updated
- 19 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25239483Zaman 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.
PubMed 35243320
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02514746
- Acronym / sponsor ID
- JEV07
- Conditions
- Encephalitis, Japanese
- Keywords
- Japanese Encephalitis Vaccines, Flavivirus Infections
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 561 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Study start
- 30 Jul 2015 (actual)
- Primary completion
- 15 Dec 2016 (actual)
- Study completion
- 12 Jan 2017 (actual)
- First posted
- 4 Aug 2015 (estimated)
- Results
- Posted 19 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV) | Experimental | Biological: Live Attenuated Japanese Encephalitis SA-14-14-2 VaccineParticipants 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. |
Who may qualify
- Ages
- 43 to 51 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Live Attenuated Japanese Encephalitis SA-14-14-2 VaccineAlso: CD-JEV, CD.JEVAX®, RS.JEV®0.5 mL subcutaneous injection | Biological | Live Attenuated JE SA-14-14-2 Vaccine (CD-JEV) |
Primary outcome
Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV
Time frame: 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
Time frame: 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.
8 secondary outcomes
Seroprotection Rate 7 Days and 28 Days After Booster Dose
Time frame: 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
Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)
Seroconversion Rate 7 Days and 28 Days After Booster Dose
Time frame: 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
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)
Number of Participants With Immediate Reactions 30 Minutes Following Booster Vaccination
Time frame: 30 minutes following booster vaccination (Study Day 365)
Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination
Time frame: 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
Time frame: 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
Time frame: 28 days following booster vaccination (Study Days 365 to 393)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25239483Zaman 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.
- Derived from this study: PubMed 35243320Zaman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
K Zaman, PhD, MPH, MBBS principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Live Attenuated Japanese Encephalitis SA-14-14-2 Vaccine in people with Encephalitis, Japanese, run by PATH.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV (time frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02514746, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.