Clinical trial NCT00249769: Determining Safety and Efficacy of Japanese Encephalitis Vaccine When Given With Measles Vaccine
Official title: Assessment of the Non-Inferiority of the Concurrent Administration of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine and Measles Vaccine Given Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Encephalitis, Japanese B
Keywords: Japanese Encephalitis
Japanese B Encephalitis
Japanese B Viral Encephalitis
Viral Encephalitis, Japanese B
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Research Institute for Tropical Medicine, Manila, Philippines
name: Quintiles, Inc.
name: Mahidol University
First posted: 2005-11-07
Enrollment: 600
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will determine whether it is safe and effective to administer Japanese encephalitis (JE) live attenuated SA 14-14-2 vaccine at the same time as measles vaccine. If it is found to be safe, it will pave the way for use in routine vaccination programs. The hypothesis is that children who receive JE live attenuated SA 14-14-2 vaccine and measles vaccine at the same time are protected against these diseases at the same level as those who receive the vaccines at different intervals.

Detailed description: Japanese encephalitis 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 Asian areas at risk 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.

An effective vaccine has existed since 1941, but has not reached the poorest countries in Asia. During the 60 years that the vaccine has been available, JE has infected an estimated 10.5 million children, resulting in more than 3 million deaths and more than 4 million children living with long-term disabilities. Control of this disease has been limited due to poor disease surveillance, a limited and unstable vaccine supply, lack of guidance and programmatic support for immunization, and limited advocacy.

A successful vaccine should be safe, efficacious, affordable, administered in a single dose, and easily incorporated into the routine Expanded Programmes on Immunization (EPI) programs. This study will help ensure the safety of SA 14-14-2 simultaneously administered with measles vaccine, paving the way for its use in routine EPI programs. If this candidate becomes widely available, it will drastically increase the feasibility of routine JE immunization in Asia, reducing the devastating death and disability caused by this disease. In addition to impacting low-income countries, the vaccine will allow countries that purchase vaccine-such as Thailand, Vietnam, Sri Lanka, and India-to recover health care dollars, improve their present programs, and address other unmet health care needs.

Eligibility criteria: Inclusion Criteria:

* Participant is healthy, aged between 8 months (± 2 weeks) at inclusion visit
* Subject is a full-term infant
* Subject's parents or legal guardian willing to provide signed informed consent.
* Children have completed 3 doses each of diphtheria, tetanus, pertussis (DTP) and oral polio vaccine (OPV).

Exclusion Criteria:

* History of documented HIV.
* Known or suspected impairment of immunologic function.
* History of serious chronic disease
* Underlying medical condition such as inborn errors of metabolism, failure to thrive, bronchopulmonary dysplasia, or any major congenital abnormalities requiring surgery or chronic treatment.
* Acute medical illness with or without fever within the last 72 hours or an axillary temperature ≥ 37.5°C at the time of inclusion.
* History of documented suspected encephalitis, encephalopathy, or meningitis
* History of measles
* History of thrombocytopenic purpura.
* Received any JE or measles vaccine prior to enrollment.
* Received any vaccine, other than the study vaccines, within 2 weeks prior to or scheduled to receive a non-study vaccination during the conduct of this trial.
* Hypotonic - hyporesponsiveness, after the preceding vaccination.
* History of seizures, including history of febrile seizures, or any other neurologic disorder.
* 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 the study vaccines. 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 enrollment.
* Suspected or known hypersensitivity to any of the investigational or marketed vaccine components.
* Serious adverse event related to the vaccine (i.e., possible, probably, definite)
* Persistent inconsolable crying (\>3 hours) observed after a previous dose.
* Unable to attend the scheduled visits or comply with the study procedures.
* Enrolled in another clinical trial involving any therapy.
* 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 Seroprotection for Measles 4 Weeks After Vaccination
timeFrame: Day 0 (before vaccination) and Day 28 (4 weeks after measles vaccination)
Secondary outcomes:
measure: Percentage of Participants With Seroprotection for Japanese Encephalitis 4 Weeks After Vaccination
timeFrame: Day 0 (before vaccination) and Day 28 (4 weeks after LJEV vaccination)
measure: Geometric Mean Concentration (GMC) of Measles Antibodies After Vaccination
timeFrame: Day 0 (before vaccination) and Day 28 (4 weeks after measles vaccination)
measure: Geometric Mean Titer (GMT) of Japanese Encephalitis Antibodies After Vaccination
timeFrame: Day 0 (before vaccination) and Day 28 (4 weeks after LJEV vaccination)
measure: Number of Participants Experiencing Local and Systemic Reactogenicity After Receiving Live Attenuated Japanese Encephalitis Vaccine (LJEV)
timeFrame: Up to 7 days after LJEV administration
measure: Number of Participants Experiencing Local and Systemic Reactogenicity After Receiving Measles Vaccine
timeFrame: Up to 7 days after measles vaccination
measure: Number of Participants Experiencing Unsolicited Adverse Events (AE)
timeFrame: Up to 7 days post-vaccination
Other outcomes:
Locations:
city: Manila
country: Philippines
facility: Research Institute for Tropical Medicine
Study officials:
affiliation: Research Institute for Tropical Medicine
name: Salvacion Gatchalian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gatchalian S, Yao Y, Zhou B, Zhang L, Yoksan S, Kelly K, Neuzil KM, Yaich M, Jacobson J. Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants. Vaccine. 2008 Apr 24;26(18):2234-41. doi: 10.1016/j.vaccine.2008.02.042. Epub 2008 Mar 18.