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

NCT01567865 | Completed Phase 4 Results

• 1 other identifier: JEV05 (VAC004)
• Study Type: interventional
• Target: 818
• Locations: 1 country
• Sites: 1

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.

Conditions

Japanese Encephalitis

Outcome Measures

Primary Outcomes (2)

• 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.

  28 days post-vaccination

• Geometric Mean Titers (GMT)

  Geometric Mean Titers of Neutralizing anti-JEV antibody

  28 days post-vaccination

Secondary Outcomes (3)

• Number/Percentage of Subjects With an Immediate Solicited Local or Systemic Reactogenicity Event (RE)

  Within 30 minutes of vaccination

• Number/Percentage of Subjects With a Solicited Local or Systemic Reactogenicity Event Within 7 Days After Vaccination

  Within 7 days of vaccination

• Number/Percentage of Subjects With Other Adverse Events (AE) During the Study

  Between 7 and 28 days of vaccination

Study Arms (4)

Reference Lot

ACTIVE COMPARATOR

Lot of Vaccine produced in existing facility

Biological: Vaccine produced in existing facility

New Lot #1

EXPERIMENTAL

First lot of vaccine produced in new facility

Biological: Vaccine produced in new facility

New Lot #2

EXPERIMENTAL

Second lot of vaccine produced in new facility

Biological: Vaccine produced in new facility

New Lot #3

EXPERIMENTAL

Third lot of vaccine produced in new facility

Biological: Vaccine produced in new facility

Interventions

Vaccine produced in existing facility BIOLOGICAL

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

Reference Lot

Vaccine produced in new facility BIOLOGICAL

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

New Lot #1; New Lot #2; New Lot #3

Eligibility Criteria

• Age: 10 Months - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

ICDDR,B

Dhaka, Bangladesh

Location

MeSH Terms

Conditions

Encephalitis, Japanese

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Mosquito-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Limitations and Caveats

Lower than anticipated rates of enrollment across all groups made it necessary to analyze antibody response data in smaller samples than initially planned. This adversely influenced the precision of all estimates (i.e., resulted in broader 95% CIs)

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• K Zaman, MD

  ICCDR,B

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 30, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 5, 2018
• Results First Posted: November 13, 2018

Record last verified: 2018-11

Locations

BA (1)