Clinical trial NCT00463476: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Japanese Encephalitis
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2007-04-20
Enrollment: 305
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
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 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.

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.

Primary outcomes:
measure: Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies
timeFrame: Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies
timeFrame: Day 0 and 28 days and 1 year post-vaccination
measure: Number of Participants With Immediate Reactions, Local and Systemic Reactions, and Unsolicited Adverse Events (AE)
timeFrame: Day 0 and 28 days and 1 year post-vaccination
measure: Number of Participants Experiencing Solicited Local Reactions Up to 3 Days Post-vaccination
timeFrame: 3 days post-vaccination
measure: Number of Participants Experiencing Solicited Systemic Reactions up to 7 Days Post-vaccination
timeFrame: 7 days post-vaccination
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: