Back to resultsLot-to-lot Consistency Trial of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine
Primary Purpose
Japanese Encephalitis
Status
Completed
Phase
Phase 4
Locations
Bangladesh
Study Type
Interventional
Intervention
Vaccine produced in existing facility
Vaccine produced in new facility
Sponsored by
About this trial
This is an interventional prevention trial for Japanese Encephalitis
Eligibility 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 enrolment residing in Matlab Health and Demographic Surveillance System (HDSS) intervention area who have completed all doses of Expanded Programme on Immunization (EPI) immunizations at least 4 weeks prior to enrolment: Bacillus Calmette-Guerin vaccine (BCG), Diphtheria-pertussis-tetanus vaccine (DPT), Hepatitis B (HBV), Haemophilus influenzae type (Hib), oral polio vaccine (OPV) and measles
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 enrolment.
- 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.
Sites / Locations
- ICDDR,B
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Arm Label
Reference Lot
New Lot #1
New Lot #2
New Lot #3
Arm Description
Lot of Vaccine produced in existing facility
First lot of vaccine produced in new facility
Second lot of vaccine produced in new facility
Third lot of vaccine produced in new facility
Outcomes
Primary Outcome Measures
Number/Percentage of Subjects With Demonstrated Seroprotection
Seroprotection was defined as a serum antibody titer equal to or greater than 1:10, as measured by Plaque reduction neutralization test (PRNT). The end point for neutralization was the highest dilution of serum reducing the number of plaques by 50%, compared with a negative serum control.
In 2004, a group of experts under the leadership of the WHO recommended that seroprotection (SP) against JEV be defined as a neutralizing anti-JEV antibody serum titer ≥1:10 as determined by PRNT [Hombach et al. 2005]. Accordingly, a titer of ≥1:10 was adopted as an indicator of seroprotection in this study.
Geometric Mean Titers (GMT)
Geometric Mean Titers of Neutralizing anti-JEV antibody
Secondary Outcome Measures
Number/Percentage of Subjects With an Immediate Solicited Local or Systemic Reactogenicity Event (RE)
Subjects were monitored for the following adverse events and categorized as events almost certainly related to receipt of the vaccine:
Redness Swelling Tenderness Dyspnea Cyanosis Loose Stools Vomiting Convulsion Fever (37 degrees Celsius or greater, axillary) Hives (urticaria) Angioedema
Number/Percentage of Subjects With a Solicited Local or Systemic Reactogenicity Event Within 7 Days After Vaccination
Collected by a home visit to observe the subject and interview his/her parent or guardian occurrence and severity of solicited injection site reactogenicity events (REs) related to vaccination and solicited systemic REs or other AEs that might or might not be related to the prior receipt of vaccine
Number/Percentage of Subjects With Other Adverse Events (AE) During the Study
Adverse events other than solicited reactogenicities were obtained through review of medical history when subject returned to clinic. They were graded for severity and rated by the PI for possible relationship to vaccination throughout the 28 days study period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01567865
Brief Title
Lot-to-lot Consistency Trial of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine
Official Title
A Clinical Trial in Healthy Infants to Assess Lot-to-lot Consistency of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine and Non-inferiority With Respect to an Earlier Product.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
4. Oversight
5. Study Description
Brief Summary
The proposed 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 Japanese Encephalitis live attenuated SA 14-14-2 vaccine (LJEVac) manufactured in a new good manufacture practice (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 aimed to enroll a total of 1,000 Bangladeshi infants aged 10 to 12 months. In addition to providing immunogenicity data, this study provided local safety data of JE live attenuated SA 14-14-2 vaccine among Bangladeshi children. This is 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Japanese Encephalitis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
818 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reference Lot
Arm Type
Active Comparator
Arm Description
Lot of Vaccine produced in existing facility
Arm Title
New Lot #1
Arm Type
Experimental
Arm Description
First lot of vaccine produced in new facility
Arm Title
New Lot #2
Arm Type
Experimental
Arm Description
Second lot of vaccine produced in new facility
Arm Title
New Lot #3
Arm Type
Experimental
Arm Description
Third lot of vaccine produced in new facility
Intervention Type
Biological
Intervention Name(s)
Vaccine produced in existing facility
Intervention Description
Live attenuated Japanese encephalitis vaccine SA 14-14-2 (LJEVac) produced in the existing facility by the Chengdu Institute of Biological Products (CDIBP), Chengdu, China
Intervention Type
Biological
Intervention Name(s)
Vaccine produced in new facility
Intervention Description
Live attenuated Japanese encephalitis vaccine SA 14-14-2 (LJEVac) produced in the new facility by the Chengdu Institute of Biological Products (CDIBP), Chengdu, China
Primary Outcome Measure Information:
Title
Number/Percentage of Subjects With Demonstrated Seroprotection
Description
Seroprotection was defined as a serum antibody titer equal to or greater than 1:10, as measured by Plaque reduction neutralization test (PRNT). The end point for neutralization was the highest dilution of serum reducing the number of plaques by 50%, compared with a negative serum control.
In 2004, a group of experts under the leadership of the WHO recommended that seroprotection (SP) against JEV be defined as a neutralizing anti-JEV antibody serum titer ≥1:10 as determined by PRNT [Hombach et al. 2005]. Accordingly, a titer of ≥1:10 was adopted as an indicator of seroprotection in this study.
Time Frame
28 days post-vaccination
Title
Geometric Mean Titers (GMT)
Description
Geometric Mean Titers of Neutralizing anti-JEV antibody
Time Frame
28 days post-vaccination
Secondary Outcome Measure Information:
Title
Number/Percentage of Subjects With an Immediate Solicited Local or Systemic Reactogenicity Event (RE)
Description
Subjects were monitored for the following adverse events and categorized as events almost certainly related to receipt of the vaccine:
Redness Swelling Tenderness Dyspnea Cyanosis Loose Stools Vomiting Convulsion Fever (37 degrees Celsius or greater, axillary) Hives (urticaria) Angioedema
Time Frame
Within 30 minutes of vaccination
Title
Number/Percentage of Subjects With a Solicited Local or Systemic Reactogenicity Event Within 7 Days After Vaccination
Description
Collected by a home visit to observe the subject and interview his/her parent or guardian occurrence and severity of solicited injection site reactogenicity events (REs) related to vaccination and solicited systemic REs or other AEs that might or might not be related to the prior receipt of vaccine
Time Frame
Within 7 days of vaccination
Title
Number/Percentage of Subjects With Other Adverse Events (AE) During the Study
Description
Adverse events other than solicited reactogenicities were obtained through review of medical history when subject returned to clinic. They were graded for severity and rated by the PI for possible relationship to vaccination throughout the 28 days study period.
Time Frame
Between 7 and 28 days of vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Months
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 enrolment residing in Matlab Health and Demographic Surveillance System (HDSS) intervention area who have completed all doses of Expanded Programme on Immunization (EPI) immunizations at least 4 weeks prior to enrolment: Bacillus Calmette-Guerin vaccine (BCG), Diphtheria-pertussis-tetanus vaccine (DPT), Hepatitis B (HBV), Haemophilus influenzae type (Hib), oral polio vaccine (OPV) and measles
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 enrolment.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K Zaman, MD
Organizational Affiliation
ICCDR,B
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICDDR,B
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
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Lot-to-lot Consistency Trial of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine
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