Lot-to-lot Consistency Trial of Japanese Encephalitis Live Attenuated SA 14-14-2 Vaccine

Phase 4

Completed

Conditions: Japanese Encephalitis

Interventions: Biological: Vaccine produced in existing facility
Biological: Vaccine produced in new facility

Registration Number: NCT01567865

Lead Sponsor: PATH

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 818

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Reference Lot	Vaccine produced in existing facility	Lot of Vaccine produced in existing facility
New Lot #1	Vaccine produced in new facility	First lot of vaccine produced in new facility
New Lot #3	Vaccine produced in new facility	Third lot of vaccine produced in new facility
New Lot #2	Vaccine produced in new facility	Second lot of vaccine produced in new facility

Primary Outcome Measures

Name	Time	Method
Number/Percentage of Subjects With Demonstrated Seroprotection	28 days post-vaccination	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)	28 days post-vaccination	Geometric Mean Titers of Neutralizing anti-JEV antibody

Secondary Outcome Measures

Name	Time	Method
Number/Percentage of Subjects With an Immediate Solicited Local or Systemic Reactogenicity Event (RE)	Within 30 minutes of vaccination	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	Within 7 days of 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	Between 7 and 28 days of vaccination	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.