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Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine

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ClinicalTrials.gov Identifier: NCT00463476
Recruitment Status : Completed
First Posted : April 20, 2007
Results First Posted : March 31, 2020
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
PATH

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.


Condition or disease Intervention/treatment Phase
Japanese Encephalitis Biological: Live, Attenuated Japanese Encephalitis SA 14-14-2 Vaccine (LJEV) Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 305 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Assessment of the Immunogenicity and Safety of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine in Children in Sri Lanka
Actual Study Start Date : July 9, 2007
Actual Primary Completion Date : November 1, 2007
Actual Study Completion Date : October 2, 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Encephalitis

Arm Intervention/treatment
Experimental: 2-year olds
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).
Biological: 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.

Experimental: 5-year olds
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).
Biological: 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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Geometric Mean Titer (GMT) of Japanese Encephalitis (JE) Neutralizing Antibodies [ Time Frame: Day 0 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%.

  2. 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 ]
    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.

  3. Number of Participants Experiencing Solicited Local Reactions Up to 3 Days Post-vaccination [ Time Frame: 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.

  4. Number of Participants Experiencing Solicited Systemic Reactions up to 7 Days Post-vaccination [ Time Frame: 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.



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Ages Eligible for Study:   2 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00463476


Locations
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Sri Lanka
Homagama MOH Division Medical Office
Homagama, District Of Colombo, Sri Lanka
Kolonnawa MOH Division Medical Office
Kolonnawa, District Of Colombo, Sri Lanka
Moratuwa MOH Division Medical Office
Moratuwa, District Of Colombo, Sri Lanka
Sponsors and Collaborators
PATH
Investigators
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Principal Investigator: Nihal Abeysinghe, MD, MSc Epidemiological Unit, Sri Lanka Ministry of Healthcare and Nutrition
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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT00463476    
Other Study ID Numbers: JEV04
First Posted: April 20, 2007    Key Record Dates
Results First Posted: March 31, 2020
Last Update Posted: March 31, 2020
Last Verified: September 2018
Additional relevant MeSH terms:
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Encephalitis, Japanese
Encephalitis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Encephalitis, Viral
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Infectious Encephalitis
Central Nervous System Infections