Immunogenicity of SA 14-14-2 JE Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT01635816
First received: July 4, 2012
Last updated: March 7, 2013
Last verified: July 2012
  Purpose

The proposed Japanese Encephalitis (JE)Vaccine study is a four-arm double-blind randomized controlled single center trial to evaluate, by examining post-vaccination seroprotection titers, the lot-to-lot consistency of three lots of JE live attenuated SA 14-14-2 vaccine manufactured in a new GMP facility, and to establish non-inferiority of the new vaccine in comparison to a single lot of the same vaccine manufactured in the existing facility. The study will enroll a total of 1,000 Bangladeshi infants aged 10 to 12 months. In addition to providing immunogenicity data, JEV05 will provide local safety data of JE live attenuated SA 14-14-2 vaccine among Bangladeshi children. This will be the first step to secure licensure for this life-saving vaccine in Bangladesh as well as provide data to support WHO prequalification of JE live attenuated SA 14-14-2 vaccine.


Condition Intervention Phase
Healthy Infants 10 - 12 Months of Age.
Biological: JE Vaccine existing facility
Biological: JE vaccine new plant lot 1
Biological: JE vaccine new plant lot 2
Biological: JE vaccine new plant lot 3
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Clinical Trial in Healthy Infants to Assess Lot-to-lot Consistency of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine Manufactured in a New Good Manufacturing Practices Facility and Non-inferiority With Respect to an Earlier Product.

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • Immunogenicity of different lots of vaccines [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    JE immunogenicity will be parameterized as the percentage of children with demonstrated seroprotection (defined as a serum antibody titer of ≥ 1:10 as measured by PRNT) at 28 days post-immunization with JE live attenuated SA 14-14-2 vaccine.


Enrollment: 1000
Study Start Date: May 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: JE Vaccine existing facilities
will receive JE live attenuated SA 14-14-2 vaccine manufactured in the existing facility (250 infants).
Biological: JE Vaccine existing facility
Will receive JE live attenuated SA 14-14-2 vaccine manufactured in the existing facility (250 infants).
Active Comparator: JE vaccine new plant lot 1
Will receive Lot 1 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Biological: JE vaccine new plant lot 1
Will receive Lot 1 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Active Comparator: JE vaccine new plant lot 2
Will receive Lot 2 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Biological: JE vaccine new plant lot 2
Will receive Lot 2 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Active Comparator: JE vaccine new plant lot 3
Will receive will receive Lot 3 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Biological: JE vaccine new plant lot 3
Will receive will receive Lot 3 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).

Detailed Description:

Vaccination is the most effective intervention to prevent JE and its associated morbidity and mortality (http://www.who.int.nuvi/Je/en). JE live attenuated SA 14-14-2 vaccine has been used in Asia for more than two decades in over 400 million children. Chengdu Institute of Biological Products (CDIBP), a Chinese manufacturer, has been producing JE live attenuated SA 14-14-2 vaccine since 1988. It has been demonstrated to be both safe and immunogenic in several observational and case-control studies providing protection for at least 5 years following a single dose. JE live attenuated SA 14-14-2 vaccine is licensed for use in China, India, Nepal, South Korea, Sri Lanka, and Thailand. Countries that have introduced JE vaccine into their national immunization programs have experienced dramatic reductions in JE incidence, leading WHO to declare vaccination the preferred JE control strategy.4

In order for JE live attenuated SA 14-14-2 vaccine to be available for purchase through UNICEF and GAVI for broader international use, including in Bangladesh, JE live attenuated SA 14-14-2 vaccine needs to undergo WHO prequalification. With technical support from PATH, CDIBP has established a new GMP facility, Building 208 JE production unit, maintaining WHO standards. A GMP Certificate for the new facility was issued on 11/16/2011. This certificate provides market authorization to distribute the new vaccine in China. To achieve WHO prequalification, JE live attenuated SA 14-14-2 vaccine produced in this new GMP facility needs to be shown to be similarly safe and immunogenic to JE live attenuated SA 14-14-2 vaccine produced in the existing facility, the JE viral vaccine production plant, and needs to demonstrate lot-to-lot consistency.

The proposed JEV05 study is a four-arm double-blind randomized controlled single center trial testing the immunogenicity of four lots of JE live attenuated SA 14-14-2 vaccine - three lots manufactured in the new GMP facility and one lot from the existing facility - in a total of 1000 Bangladeshi infants aged 10 to 12 months. The study will be conducted in the Matlab Health and Demographic Surveillance System (HDSS) intervention area, a rural site where many vaccine trials have been conducted.

A 5 ml blood sample will be collected from each child before vaccination and at 28 days post-vaccination. The sera will be tested using a plaque reduction neutralization test (PRNT) with JE neutralizing antibody titers > 1:10 considered seroprotective. The JEV05 trial will provide immunogenicity data on the three vaccine lots produced in the new GMP facility compared to a vaccine lot produced in the prior existing plant. It will also provide local immunogenicity and safety data of JE live attenuated SA 14-14-2 vaccine among Bangladeshi children. This will be the first step to secure licensure for this life-saving vaccine in Bangladesh as well as provide data to support WHO prequalification of JE live attenuated SA 14-14-2 vaccine.

  Eligibility

Ages Eligible for Study:   10 Months to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Infant's parent(s) or legal guardian(s) willing to provide signed informed consent.
  • Healthy infants aged 10 to 12 months at enrollment residing in Matlab HDSS intervention area who have completed all doses of EPI immunizations (BCG, DPT, HBV, Hib, OPV and measles) at least 4 weeks prior to enrollment.

Exclusion Criteria:

  • Acute medical illness with or without fever within the last 72 hours or an axillary temperature (≥ 37.5°C ) at the time of vaccination.
  • Use of antibiotics or antipyretics within the last 72 hours prior to enrollment.
  • Severely or moderately malnourished infants (<-3 Z score).
  • History of prematurity (< 36 weeks of pregnancy).
  • Underlying medical condition such as failure to thrive, inborn errors of metabolism, bronchopulmonary dysplasia, or any major congenital abnormalities requiring surgery or chronic treatment.
  • History of serious chronic disease (e.g., cardiac, renal, neurologic, metabolic, rheumatologic, hematologic, or bleeding disorder).
  • Known or suspected impairment of immunologic function.
  • History of documented or suspected encephalitis or meningitis.
  • History of seizures, including history of febrile seizures, or any other neurologic disorder.
  • History of JE infection.
  • Prior receipt of a JE vaccine.
  • Received measles vaccine within 4 weeks prior to, or scheduled to receive a vaccination during, the conduct of this trial.
  • Prior or anticipated receipt of immune globulin or other blood products, or injected or oral corticosteroids or other immune modulator therapy within 6 weeks of administration of the study vaccine.
  • Serious adverse reactions (e.g. urticaria, angioedema, shock, breathlessness following vaccination or any life threatening condition) with any previous EPI vaccine.
  • 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 child, or interfere with the evaluation of the study objectives.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01635816

Locations
Bangladesh
Matlab
Chandpur, Bangladesh
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

No publications provided

Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT01635816     History of Changes
Other Study ID Numbers: PR-11050
Study First Received: July 4, 2012
Last Updated: March 7, 2013
Health Authority: Bangladesh: Ethical Review Committee

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Immunogenicity
SA 14-14-2 JE vaccine
Bangladesh

Additional relevant MeSH terms:
Encephalitis, Japanese
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on July 24, 2014