- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00463684
Live Attenuated Japanese Encephalitis (JE) Vaccine Coadministered With Measles Vaccine in Infants 9 Months of Age (JEV03)
September 11, 2018 updated by: PATH
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 at 9 months of age.
The primary hypothesis was that the seropositivity rate at 28 days post vaccination in Japanese Encephalitis (JE) and measles concomitantly vaccinated subjects 9 months of age is greater than 80% for JE and greater than 90% for measles.
Study Overview
Status
Completed
Conditions
Detailed Description
JE virus is an arbovirus that causes a devastating neurological disease resulting in high rates of mortality orneurologic 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.
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.
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.
For Sri Lanka, switching to the less expensive LJEV was estimated in 2006 to save the National Immunization Programme (NIP) between US$8.6 and $8.9 million annually in direct vaccine costs alone.
To generate local immunogenicity and safety data to guide policy for potential use of LJEV in Sri Lanka's NIP, the Ministry of Healthcare and Nutrition, in cooperation with PATH, initiated the study.
The study was conducted in three peri-urban health divisions of low JE endemicity in the District of Colombo.
Study Type
Interventional
Enrollment (Actual)
278
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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District Of Colombo
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Homagama, District Of Colombo, Sri Lanka
- Homagama MOH Division Medical Office
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Kolonnawa, District Of Colombo, Sri Lanka
- Kolonnawa MOH Division Medical Office
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Moratuwa, District Of Colombo, Sri Lanka
- Moratuwa MOH Division Medical Office
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
9 months to 9 months (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy child 9 months (±2 weeks) 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: All subjects
Healthy infants 9 months of age (plus or minus 2 weeks) that met the eligibility criteria.
Subjects received one dose of Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) and one dose of live, attenuated measles vaccine.
|
Manufactured by Chengdu Institute of Biological Products (CDIBP), Chengdu, China; batch 200611A078-1.
Administered subcutaneously in the right brachium.
Manufactured by Serum Institute of India, Ltd, Pune, India; batch EU3244.
Administered subcutaneously in the left brachium.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number and Percentage of Subjects With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
Time Frame: 1 year
|
Blood serum was collected immediately before administration (Day 0), Day 28, six months post-administration, 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.
|
1 year
|
Number and Percentage of Subjects With Demonstrated Seropositivity for Anti-measles Immunoglobulin G (IgG): Manufacturer Definition
Time Frame: 1 year
|
Blood serum was collected immediately before administration (Day 0), Day 28, six months post-administration, and 1 year later.
Serum anti-measles immunoglobulin class G (IgG) antibodies were measured by enzyme-linked immunosorbent assay (ELISA) (Serion ELISA classic Measles Virus IgG, Serion GmbH, Würzburg,Germany).
For anti-measles IgG, two definitions of seropositivity were used: per manufacturer's instruction (concentration of>200 mIU/mL, this table) and when including those with "borderline" results (≥150 mIU/mL).
|
1 year
|
Number and Percentage of Subjects With Demonstrated Seropositivity for Anti-measles Immunoglobulin G (IgG): Including Borderline Subjects
Time Frame: 1 year
|
Blood serum was collected immediately before administration (Day 0), Day 28, six months post-administration, and 1 year later.
Serum anti-measles immunoglobulin class G (IgG) antibodies were measured by enzyme-linked immunosorbent assay (ELISA) (Serion ELISA classic Measles Virus IgG, Serion GmbH, Würzburg,Germany).
For anti-measles IgG, two definitions of seropositivity were used: per manufacturer's instruction (concentration of>200 mIU/mL) and when including those with "borderline" results (≥150 mIU/mL, this table).
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
Time Frame: 1 year
|
Blood serum was collected immediately before administration (Day 0), Day 28, six months post-administration, 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%.
|
1 year
|
Geometric Mean Titer (GMT) of Anti-measles Immunoglobulin G (IgG)
Time Frame: 1 year
|
Blood serum was collected immediately before administration (Day 0), Day 28, six months post-administration, and 1 year later.
Serum anti-measles immunoglobulin class G (IgG) antibodies were measured by enzyme-linked immunosorbent assay (ELISA) (Serion ELISA classic Measles Virus IgG, Serion GmbH, Würzburg,Germany).
For anti-measles IgG, two definitions of seropositivity were used: per manufacturer's instruction (concentration of>200 mIU/mL, this table) and when including those with "borderline" results (≥150 mIU/mL).
|
1 year
|
Number and Percentage of Subjects With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
Time Frame: 1 year
|
Subjects 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 subjects' parents 2 days after vaccination and monthly through 1 year to inquire about the child's well being and review the diary card.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
The subject 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.
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1 year
|
Number of Solicited Local Reactions to LJEV: Days 0-3
Time Frame: 3 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
|
3 days
|
Number of Solicited Local Reactions to LJEV: Days 4-7
Time Frame: 4 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
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4 days
|
Number of Solicited Local Reactions to Measles Vaccine: Days 0-3
Time Frame: 3 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
|
3 days
|
Number of Solicited Local Reactions to Measles Vaccine: Days 4-7
Time Frame: 4 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
|
4 days
|
Number of Solicited Systemic Reactions: Days 0-3
Time Frame: 3 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
|
3 days
|
Number of Solicited Systemic Reactions: Days 4-7
Time Frame: 4 days
|
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 after vaccination.
The subject was visited at home on Day 7 to review and collect the reactogenicity diary card.
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4 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Nihal Abeysinghe, MD, MSc, Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 7, 2007
Primary Completion (Actual)
November 7, 2007
Study Completion (Actual)
October 6, 2008
Study Registration Dates
First Submitted
April 18, 2007
First Submitted That Met QC Criteria
April 18, 2007
First Posted (Estimate)
April 20, 2007
Study Record Updates
Last Update Posted (Actual)
February 8, 2019
Last Update Submitted That Met QC Criteria
September 11, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Encephalitis, Arbovirus
- Encephalitis, Viral
- Central Nervous System Viral Diseases
- Central Nervous System Infections
- Infectious Encephalitis
- Arbovirus Infections
- Vector Borne Diseases
- Flavivirus Infections
- Flaviviridae Infections
- Encephalitis, Japanese
- Encephalitis
- Physiological Effects of Drugs
- Immunologic Factors
- Vaccines
Other Study ID Numbers
- JEV03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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