Back to resultsBoosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine
Primary Purpose
Japanese Encephalitis
Status
Completed
Phase
Phase 4
Locations
Sri Lanka
Study Type
Interventional
Intervention
Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)
Sponsored by
About this trial
This is an interventional prevention trial for Japanese Encephalitis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- Homagama MOH Division Medical Office
- Kolonnawa MOH Division Medical Office
- Moratuwa MOH Division Medical Office
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
2-year olds
5-year olds
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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%.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00463476
Brief Title
Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine
Official Title
Assessment of the Immunogenicity and Safety of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine in Children in Sri Lanka
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
July 9, 2007 (Actual)
Primary Completion Date
November 1, 2007 (Actual)
Study Completion Date
October 2, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Japanese Encephalitis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
305 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2-year olds
Arm Type
Experimental
Arm Description
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).
Arm Title
5-year olds
Arm Type
Experimental
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV)
Intervention Description
Manufactured by Chengdu Institute of Biological Products (CDIBP), Chengdu, China; batch 200611A078-1. Administered subcutaneously in the right upper arm using 23 gauge needles.
Primary Outcome Measure Information:
Title
Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
Description
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.
Time Frame
Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination
Secondary Outcome Measure Information:
Title
Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
Description
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%.
Time Frame
Day 0 and 28 days and 1 year post-vaccination
Title
Number of Participants With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
Description
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.
Time Frame
Day 0 and 28 days and 1 year post-vaccination
Title
Number of Participants Experiencing Solicited Local Reactions Up to 3 Days Post-vaccination
Description
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.
Time Frame
3 days post-vaccination
Title
Number of Participants Experiencing Solicited Systemic Reactions up to 7 Days Post-vaccination
Description
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.
Time Frame
7 days post-vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nihal Abeysinghe, MD, MSc
Organizational Affiliation
Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
Official's Role
Principal Investigator
Facility Information:
Facility Name
Homagama MOH Division Medical Office
City
Homagama
State/Province
District Of Colombo
Country
Sri Lanka
Facility Name
Kolonnawa MOH Division Medical Office
City
Kolonnawa
State/Province
District Of Colombo
Country
Sri Lanka
Facility Name
Moratuwa MOH Division Medical Office
City
Moratuwa
State/Province
District Of Colombo
Country
Sri Lanka
12. IPD Sharing Statement
Learn more about this trial
Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine
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