Clinical trial NCT00463684: Live Attenuated Japanese Encephalitis (JE) Vaccine Coadministered With Measles Vaccine in Infants 9 Months of Age
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Japanese Encephalitis
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Ministry of Health of Sri Lanka
name: Mahidol University
name: Quintiles Singapore
First posted: 2007-04-20
Enrollment: 278
Sex: ALL
Minimum age (years): 9
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number and Percentage of Subjects With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
timeFrame: 1 year
measure: Number and Percentage of Subjects With Demonstrated Seropositivity for Anti-measles Immunoglobulin G (IgG): Manufacturer Definition
timeFrame: 1 year
measure: Number and Percentage of Subjects With Demonstrated Seropositivity for Anti-measles Immunoglobulin G (IgG): Including Borderline Subjects
timeFrame: 1 year
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
timeFrame: 1 year
measure: Geometric Mean Titer (GMT) of Anti-measles Immunoglobulin G (IgG)
timeFrame: 1 year
measure: Number and Percentage of Subjects With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
timeFrame: 1 year
measure: Number of Solicited Local Reactions to LJEV: Days 0-3
timeFrame: 3 days
measure: Number of Solicited Local Reactions to LJEV: Days 4-7
timeFrame: 4 days
measure: Number of Solicited Local Reactions to Measles Vaccine: Days 0-3
timeFrame: 3 days
measure: Number of Solicited Local Reactions to Measles Vaccine: Days 4-7
timeFrame: 4 days
measure: Number of Solicited Systemic Reactions: Days 0-3
timeFrame: 3 days
measure: Number of Solicited Systemic Reactions: Days 4-7
timeFrame: 4 days
Other outcomes:
Locations:
city: Homagama
country: Sri Lanka
facility: Homagama MOH Division Medical Office
state: District Of Colombo
city: Kolonnawa
country: Sri Lanka
facility: Kolonnawa MOH Division Medical Office
state: District Of Colombo
city: Moratuwa
country: Sri Lanka
facility: Moratuwa MOH Division Medical Office
state: District Of Colombo
Study officials:
affiliation: Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
name: Nihal Abeysinghe, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: