Japanese EncephalitisPhase 4NCT00463476
Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine
A Phase 4 study testing Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) in people with Japanese Encephalitis, run by PATH at 3 sites in Sri Lanka.
Trial summary
To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine in children at 2 and 5 years of age. Read more about this study
- Who is it for?
- Ages 2 to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- Japanese Encephalitis
- What is being tested?
- Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 305 participants
- Where
- 3 sitesSri Lanka
- Study dates
- 9 Jul 2007to 2 Oct 2008
- 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 2 to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy child 2 years (±3 months) or 5 years (±3 months) of age at the enrollment visit.
- Subject was a full-term infant.
- Subject's parent or legal guardian is literate and willing to provide written informed consent.
- Subject is up-to-date for all vaccinations recommended in the Sri Lankan childhood immunization schedule.
Who cannot join
- Enrolled in another clinical trial involving any therapy.
- Subject and/or parent(s) or guardian(s) are unable to attend the scheduled visits or comply with the study procedures.
- Received any non-study vaccine within 2 weeks prior to enrolment or refusal to postpone receipt of such vaccines until 28 days after study entry.
- Prior or anticipated receipt of immune globulin or other blood products, or injected or oral corticosteroids or other immune modulator therapy except routine vaccines within 6 weeks of administration of study vaccine. Individuals on a tapering dose schedule of oral steroids lasting <7 days may be included in the trial as long as they have not received more than one course within the last 2 weeks prior to enrolment.
- History of documented or suspected encephalitis, encephalopathy, or meningitis.
- History of measles.
Show all 18Show fewer
- History of Japanese encephalitis.
- Serious adverse event related (i.e., possible, probably, definite) to previous receipt of any JE vaccine, if applicable.
- Persistent inconsolable crying (>3 hours) observed after previous receipt of any JE vaccine, if applicable.
- Hypotonic - hyporesponsiveness after past receipt of any JE vaccine, if applicable.
- Suspected or known hypersensitivity to any of the investigational or marketed vaccine components.
- History of serious chronic disease (cardiac, renal, neurologic, metabolic, or rheumatologic).
- Underlying medical condition such as inborn errors of metabolism, failure to thrive, bronchopulmonary dysplasia, or any major congenital abnormalities requiring surgery or chronic treatment.
- History of thrombocytopenic purpura.
- History of seizures, including history of febrile seizures, or any other neurologic disorder.
- Known or suspected immunologic function impairment of any kind and/or known HIV infection.
- Parent with known or suspected immunologic function impairment of any kind and/or known HIV infection.
- Any condition that, in the opinion of the investigator, would pose a health risk to the participant or interfere with the evaluation of the study objectives.
Trial locations and contacts
3 sites in 1 country.
Sri Lanka3 sites
Homagama MOH Division Medical Office
Homagama, District of Colombo
Kolonnawa MOH Division Medical Office
Kolonnawa, District of Colombo
Moratuwa MOH Division Medical Office
Moratuwa, District of Colombo
About this study
Official title: Assessment of the Immunogenicity and Safety of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine in Children in Sri Lanka
To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine in children at 2 and 5 years of age. The primary hypothesis was that the seropositivity rate at 28 days post vaccination of SA 14-14-2 in subjects 2 and 5 years of age who have already received at least two doses of mouse brain-derived inactivated JE vaccine is greater than 80%.
Japanese encephalitis virus is the leading cause of viral neurological disease and disability in Asia. The severity of sequelae, together with the volume of cases, make JE the most important cause of viral encephalitis in the world. Approximately 3 billion people-including 700 million children-live in areas at risk in Asia for JE. JE most commonly infects children between the ages of 1 and 15 years, and can also infect adults in areas where the virus is newly introduced. More than 50,000 cases are reported annually and cause an estimated 10,000 to 15,000 deaths. This figure is believed to represent only a small proportion of the disease burden that actually exists.
Read the detailed description
JE virus is an arbovirus that causes a devastating neurological disease resulting in high rates of mortality or neurologic sequelae. The severity of sequelae, together with the volume of cases, makes JE an important cause of encephalitis. The disease is endemic across temperate and tropical zones of Asia,and because of its zoonotic cycle, eradicating JE from the environment is unrealistic. Universal childhood vaccination is essential for disease control.
Concern in Japan over a rare but potentially dangerous adverse event associated with a mouse brain-derived vaccine led the manufacturer in Japan to discontinue production in 2005, thus limiting global supply of inactivated JE vaccines and raising costs for remaining inactivated vaccines. In August of 2006, the World Health Organization stated in its position paper on Japanese encephalitis vaccines that the mouse brain-derived vaccine should be replaced by a new generation of JE vaccines.
In Sri Lanka, immunization against JE began in 1988. By 2006, two types of JE vaccines were available for use in Sri Lanka-inactivated mouse brain-derived vaccine and live attenuated SA-14-14-2 JE vaccine (LJEV). Only the inactivated vaccine was being used in the country's public-sector immunization program. It is given to children in 3 doses, at 12 months of age, 13 months of age, and 2 years of age. A booster dose must also be given to children at 5 years of age. If Sri Lanka decides to replace the inactivated JE vaccine with the live attenuated JE vaccine, there will be many children who still need a 3rd or booster dose of the inactivated JE vaccine. This research study was done to see if the live attenuated vaccine would work well to replace the inactivated JE vaccine and if it is safe in Sri Lankan children. The study was conducted in three peri-urban health divisions of low JE endemicity in the District of Colombo.
- Conditions
- Japanese Encephalitis
- Being tested
- Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)
- Medical subject headings
- Encephalitis, Japanese
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 Vaccine (LJEV)Biological
Manufactured by Chengdu Institute of Biological Products (CDIBP), Chengdu, China; batch 200611A078-1. Administered subcutaneously in the right upper arm using 23 gauge needles.
| Study group | Role | What they receive |
|---|---|---|
| 2-year olds | Experimental | Healthy children 2 years of age (±3 months) who had previously received all vaccinations recommended under the Sri Lankan childhood immunization schedule according to their age. Subjects must have previously received inactivated mouse brain-derived Japanese Encephalitis vaccine (IMBV) at the recommended 12 and 13 months of age. Subjects received one dose of Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV). Receives: Biological: Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) |
| 5-year olds | Experimental | Healthy children 5 years of age (±3 months) that met all other eligibility criteria. Subjects must have previously received inactivated mouse brain-derived Japanese Encephalitis vaccine (IMBV) at the recommended 12, 13, and 24 months of age. Subjects received one dose of Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV). Receives: Biological: Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
Blood serum was collected immediately before administration (Day 0), Day 28, and 1 year later. Serum neutralizing antibodies to the Beijing-1 JE strain were measured by plaque reduction neutralization test (PRNT) where the neutralizing titer was measured as the inverse dilution at which plaque counts were reduced by 50%. Seropositivity was defined as a titer of ≥ 1:10.
Measured: Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination
Secondary outcomes (4)
Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
Blood serum was collected immediately before administration (Day 0), Day 28, and 1 year later. Serum neutralizing antibodies to the Beijing-1 JE strain were measured by plaque reduction neutralization test (PRNT) where the neutralizing titer was measured as the inverse dilution at which plaque counts were reduced by 50%.
Measured: Day 0 and 28 days and 1 year post-vaccination
Number of Participants With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
Participants were monitored for immediate AEs and local reactions for 30 minutes after each injection by a study physician. Thereafter, parents recorded axillary temperature, local reactions (redness, swelling, pain, and other local reactions), and systemic symptoms (high-grade fever, anorexia, crying, diarrhea, drowsiness, insomnia, irritability, vomiting, and other systemic symptoms) in a study diary for 7 days afterwards. Study staff called the participants' parents 2 days after vaccination and monthly through 1 year to inquire about the child's well being and review the diary card. The participant was visited at home on Day 7 to review and collect the reactogenicity diary card. The participant returned to the vaccination clinic on Day 28, 6 months, and 1 year to be examined, have a blood draw, and review any AEs or serious adverse events (SAE) with parents.
Measured: Day 0 and 28 days and 1 year post-vaccination
Number of Participants Experiencing Solicited Local Reactions Up to 3 Days Post-vaccination
Parents recorded local reactions (redness, swelling, pain, and other local reactions) in a study diary.
Events were assessed by the clinician to quantify intensity using the following guidelines:
- Mild: Events required minimal or no treatment and do not interfere with the child's functioning.
- Moderate: Events resulted in a low level of concern with therapeutic measures. Moderate events may cause some interference with functioning.
- Severe: Events interrupted the child's functioning and may have required systemic drug therapy or other treatment. Severe events are usually incapacitating.
Measured: 3 days post-vaccination
Number of Participants Experiencing Solicited Systemic Reactions up to 7 Days Post-vaccination
Parents recorded axillary temperature and systemic symptoms (high-grade fever, anorexia, crying, diarrhea, drowsiness, insomnia, irritability, vomiting, and other systemic symptoms) in a study diary for 7 days after vaccination. The participant was visited at home on Day 7 to review and collect the reactogenicity diary card.
Events were assessed by the clinician to quantify intensity using the following guidelines:
- Mild: Events required minimal or no treatment and do not interfere with the child's functioning.
- Moderate: Events resulted in a low level of concern with therapeutic measures. Moderate events may cause some interference with functioning.
- Severe: Events interrupted the child's functioning and may have required systemic drug therapy or other treatment. Severe events are usually incapacitating.
Measured: 7 days post-vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2007 (estimated)
- Study start9 Jul 2007
- Primary completion1 Nov 2007
- Study completion2 Oct 2008
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.
- Other trials for Japanese EncephalitisStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 305 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nihal Abeysinghe, MD, MSc, Principal investigator, Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00463476
- Sponsor's protocol ID
- JEV04
- Status last verified
- Sep 2018
- First submitted
- 18 Apr 2007
- Last updated
- 31 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Immunogenicity and Safety of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine in Children in Sri Lanka
- ClinicalTrials.gov ID
- NCT00463476
- Acronym / sponsor ID
- JEV04
- Conditions
- Japanese Encephalitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Study start
- 9 Jul 2007 (actual)
- Primary completion
- 1 Nov 2007 (actual)
- Study completion
- 2 Oct 2008 (actual)
- First posted
- 20 Apr 2007 (estimated)
- Results
- Posted 31 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine in children at 2 and 5 years of age. The primary hypothesis was that the seropositivity rate at 28 days post vaccination of SA 14-14-2 in subjects 2 and 5 years of age who have already received at least two doses of mouse brain-derived inactivated JE vaccine is greater than 80%.
Japanese encephalitis virus is the leading cause of viral neurological disease and disability in Asia. The severity of sequelae, together with the volume of cases, make JE the most important cause of viral encephalitis in the world. Approximately 3 billion people-including 700 million children-live in areas at risk in Asia for JE. JE most commonly infects children between the ages of 1 and 15 years, and can also infect adults in areas where the virus is newly introduced. More than 50,000 cases are reported annually and cause an estimated 10,000 to 15,000 deaths. This figure is believed to represent only a small proportion of the disease burden that actually exists.
Detailed description
JE virus is an arbovirus that causes a devastating neurological disease resulting in high rates of mortality or neurologic sequelae. The severity of sequelae, together with the volume of cases, makes JE an important cause of encephalitis. The disease is endemic across temperate and tropical zones of Asia,and because of its zoonotic cycle, eradicating JE from the environment is unrealistic. Universal childhood vaccination is essential for disease control.
Concern in Japan over a rare but potentially dangerous adverse event associated with a mouse brain-derived vaccine led the manufacturer in Japan to discontinue production in 2005, thus limiting global supply of inactivated JE vaccines and raising costs for remaining inactivated vaccines. In August of 2006, the World Health Organization stated in its position paper on Japanese encephalitis vaccines that the mouse brain-derived vaccine should be replaced by a new generation of JE vaccines.
In Sri Lanka, immunization against JE began in 1988. By 2006, two types of JE vaccines were available for use in Sri Lanka-inactivated mouse brain-derived vaccine and live attenuated SA-14-14-2 JE vaccine (LJEV). Only the inactivated vaccine was being used in the country's public-sector immunization program. It is given to children in 3 doses, at 12 months of age, 13 months of age, and 2 years of age. A booster dose must also be given to children at 5 years of age. If Sri Lanka decides to replace the inactivated JE vaccine with the live attenuated JE vaccine, there will be many children who still need a 3rd or booster dose of the inactivated JE vaccine. This research study was done to see if the live attenuated vaccine would work well to replace the inactivated JE vaccine and if it is safe in Sri Lankan children. The study was conducted in three peri-urban health divisions of low JE endemicity in the District of Colombo.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2-year olds | Experimental | Biological: Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)Healthy children 2 years of age (±3 months) who had previously received all vaccinations recommended under the Sri Lankan childhood immunization schedule according to their age. Subjects must have previously received inactivated mouse brain-derived Japanese Encephalitis vaccine (IMBV) at the recommended 12 and 13 months of age. Subjects received one dose of Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV). |
| 5-year olds | Experimental | Biological: Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)Healthy children 5 years of age (±3 months) that met all other eligibility criteria. Subjects must have previously received inactivated mouse brain-derived Japanese Encephalitis vaccine (IMBV) at the recommended 12, 13, and 24 months of age. Subjects received one dose of Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV). |
Who may qualify
- Ages
- 2 to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Healthy child 2 years (±3 months) or 5 years (±3 months) of age at the enrollment visit.
- Subject was a full-term infant.
- Subject's parent or legal guardian is literate and willing to provide written informed consent.
- Subject is up-to-date for all vaccinations recommended in the Sri Lankan childhood immunization schedule.
Key exclusion criteria (18 listed)
- Enrolled in another clinical trial involving any therapy.
- Subject and/or parent(s) or guardian(s) are unable to attend the scheduled visits or comply with the study procedures.
- Received any non-study vaccine within 2 weeks prior to enrolment or refusal to postpone receipt of such vaccines until 28 days after study entry.
- Prior or anticipated receipt of immune globulin or other blood products, or injected or oral corticosteroids or other immune modulator therapy except routine vaccines within 6 weeks of administration of study vaccine. Individuals on a tapering dose schedule of oral steroids lasting <7 days may be included in the trial as long as they have not received more than one course within the last 2 weeks prior to enrolment.
- History of documented or suspected encephalitis, encephalopathy, or meningitis.
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 Vaccine (LJEV)Manufactured by Chengdu Institute of Biological Products (CDIBP), Chengdu, China; batch 200611A078-1. Administered subcutaneously in the right upper arm using 23 gauge needles. | Biological | 2-year olds, 5-year olds |
Primary outcome
Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
Time frame: Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination
Blood serum was collected immediately before administration (Day 0), Day 28, and 1 year later. Serum neutralizing antibodies to the Beijing-1 JE strain were measured by plaque reduction neutralization test (PRNT) where the neutralizing titer was measured as the inverse dilution at which plaque counts were reduced by 50%. Seropositivity was defined as a titer of ≥ 1:10.
4 secondary outcomes
Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
Time frame: Day 0 and 28 days and 1 year post-vaccination
Number of Participants With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
Time frame: Day 0 and 28 days and 1 year post-vaccination
Number of Participants Experiencing Solicited Local Reactions Up to 3 Days Post-vaccination
Time frame: 3 days post-vaccination
Number of Participants Experiencing Solicited Systemic Reactions up to 7 Days Post-vaccination
Time frame: 7 days post-vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Nihal Abeysinghe, MD, MSc principal investigator
Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) in people with Japanese Encephalitis, run by PATH at 3 sites in Sri Lanka.
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 4 inclusion and 18 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 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sri Lanka. Whether a site is taking part right now should be confirmed with that site. See every site.
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 31 Mar 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?
Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies (time frame: Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Mar 2020.