Immunogenicity of a JE-CV as a Booster Dose After a Primary Vaccination With SA14-14-2 Vaccine

Sponsor

Chulalongkorn University (Other)

Overall Status

Completed

CT.gov ID

NCT02602652

Collaborator

Sanofi Pasteur, a Sanofi Company (Industry)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

The objective of this study is to measured the Geometric mean titer (GMT) of Japanese Encephalitis neutralizing antibody and proportion of seroprotection among the children who received a booster dose of JE-CV after the first dose of SA14-14-2 vaccine.

Condition or Disease	Intervention/Treatment	Phase
Japanese Encephalitis	Biological: a live attenuated chimeric JE vaccine	N/A

Detailed Description

Study design: This open label clinical trial in 50 children aged 1-5 years, was conducted at King Chulalongkorn Memorial Hospital in Thailand. The protocol was approved by the Institutional Review Board of Chulalongkorn University, and the study was performed in accordance with Declaration of Helsinki, International Conference on Harmonization Good Clinical Practice, the European Directive 2001/20/EC, and written informed consent was obtained from parents or a legally acceptable representative before enrolment.

Vaccines: JE-CV was manufactured by Sanofi Pasteur Biologics Co., USA., and reconstituted using 0.4% sodium chloride diluent for injection; each dose 0.5 ml contained 4.0-5.8 log10 plaque forming units of virus Serology: JE neutralizing antibody levels were assessed using a PRNT50 assay. The final end point neutralization titer is the inverse of the highest serial dilution of serum that can neutralize ≥ 50% of JE challenge virus. Testing was performed at Focus Diagnostics Inc. using JE-CV as a challenge virus.

Statistical methods: sample size was calculated based on historical data from JE15 study, at month 24 after first dose of JE-CV, the GMT of JE neutralizing antibody was 39.4 (95% CI 33.7 to 46.0) and increase to 2242 (95% CI 1913, 2628) at day 28 post JE-CV booster dose. On the assumption that children who received SA14-14-2 vaccine and subsequently get one booster dose of JE-CV at 12-24 months later will have GMT of at least 1040, with 80% power and alpha 0.05, data at least 43 children need to be collected. When accounted for 15% of children who might loss to follow-up or cannot get adequate blood sample, 50 children should be enrolled.

The per-protocol population will be used for the main immunogenicity analyses. For the main parameters, 95% confidence intervals (CIs) of point estimates will be calculated using the normal approximation for quantitative data and the exact binomial distribution for proportions. The point estimates and their 95% CI of the following will be presented for each group of the Geometric Mean (GM) of neutralizing antibody on D0 and D28 and the percentage of subjects with neutralizing antibody >=10 at D0 and D28

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Immunogenicity of a Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) as a Booster Dose After a Primary Vaccination With SA14-14-2 Vaccine in Thai Children

Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: a live attenuated chimeric JE vaccine Children were received JE-CV as a booster dose after vaccinated with SA14-14-2 vaccine as a first dose regimen 12-24 months before.	Biological: a live attenuated chimeric JE vaccine The study included 2 visits (D0 and D28). At the first visit (D0), children were enrolled, collected the blood sample for evaluate the baseline immune status and given a JE-CV as a booster dose. After vaccination, children were observed for 30 minutes to monitor any immediate adverse events. Parents were given a digital thermometer for axillary temperature measurement, a ruler for measuring injection site reactions and a diary card for recording a solicited injection site and systemic reactions. At the second visit (D28), blood samples were collected for evaluate the immunogenicity. Other Names: Japanese Encephalitis Chimeric Virus vaccine

Arm

Intervention/Treatment

Experimental: a live attenuated chimeric JE vaccine

Children were received JE-CV as a booster dose after vaccinated with SA14-14-2 vaccine as a first dose regimen 12-24 months before.

Biological: a live attenuated chimeric JE vaccine

The study included 2 visits (D0 and D28). At the first visit (D0), children were enrolled, collected the blood sample for evaluate the baseline immune status and given a JE-CV as a booster dose. After vaccination, children were observed for 30 minutes to monitor any immediate adverse events. Parents were given a digital thermometer for axillary temperature measurement, a ruler for measuring injection site reactions and a diary card for recording a solicited injection site and systemic reactions. At the second visit (D28), blood samples were collected for evaluate the immunogenicity.

Other Names:

Japanese Encephalitis Chimeric Virus vaccine

Outcome Measures

Primary Outcome Measures

Changing in geometric mean titer of JE neutralizing antibody at day 0 pre-vaccination and day 28 post vaccination. [day 0 pre-vaccination and day 28 post vaccination]

Secondary Outcome Measures

Proportion of children who had seroprotection at day 0 pre-vaccination and day 28 post vaccination [day 0 pre-vaccination and day 28 post vaccination]
seroprotection defined as titer ≥10

Other Outcome Measures

JE-CV related adverse reaction [28 days]
Solicited injection site reactions: redness (in proportion of children) swelling (in proportion of children) pain (in proportion of children) Systemic solicited reactions: (measure in proportion of children) Unsolicited adverse reactions (measure in proportion of children)

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 5 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

1 Children aged 1 to <5 years on the day of inclusion

History of received 1 dose of SA14-14-2 vaccine 12-24 months prior to enrollment
In good general health at the time of inclusion
Provision of informed consent by the parent(s) or legal guardian(s)