search
Back to results

Study of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Children Previously Immunized With JE-CV

Primary Purpose

Japanese Encephalitis, Varicella

Status
Completed
Phase
Phase 3
Locations
Philippines
Study Type
Interventional
Intervention
JE-CV Vaccine
Varicella Vaccine
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Japanese Encephalitis focused on measuring Japanese Encephalitis, Japanese encephalitis chimeric virus vaccine, Varicella, Varicella vaccine

Eligibility Criteria

36 Months - 42 Months (Child)All SexesAccepts Healthy Volunteers

An individual had to fulfill all of the following criteria in order to be eligible for trial enrollment:

All Participants

  • Aged 36 to 42 months on the day of inclusion
  • Provision of Informed Consent Form signed by at least one parent or other legally acceptable representative
  • Participant and parent/legally acceptable representative or guardian able to attend all scheduled visits and to comply with all trial procedures
  • In good general health, based on medical history and physical examination

For JE-CV vaccine primed group only

  • Participant who was vaccinated with JE-CV in JEC02 trial (NCT00735644)

An individual fulfilling any of the following criteria was excluded from trial enrollment:

All Participants

  • Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial vaccination
  • Planned participation in another clinical trial during the Day 0 - Month 6 period and for Group 1 up to 5 years for any flavivirus vaccine trial
  • Receipt of any vaccine* in the 4 weeks preceding the trial vaccination, except for pandemic influenza vaccination, which may be received at least 2 weeks before study vaccines
  • Planned receipt of any vaccine* in the 4 weeks following the trial vaccination, except for pandemic influenza vaccine. In the event of local or national immunization program with a pandemic influenza vaccine, participants who receive a pandemic influenza vaccine at any time during the trial will not be withdrawn from the trial.
  • Planned receipt of any JE vaccine during the course of the trial
  • Administration of any anti-viral within 2 months preceding the trial vaccination and up to 4 weeks following the trial vaccination
  • Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
  • Seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, as reported by the parent/legally acceptable representative
  • History of central nervous system disorder or disease, including seizures and febrile seizures
  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
  • Chronic illness or any underlying illness (such as cardiovascular, kidney, liver or hematological disease or development abnormalities) that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion

    • Except in case of national immunization days with oral polio vaccine

For JE-CV primed participants only

  • Receipt of any JE vaccine other than JE-CV during JEC02 trial(NCT00735644) and since the end of JEC02 trial

For JE-CV naïve participants only

  • Previous vaccination against flavivirus disease including JE
  • History of flavivirus infection either based on clinical suspicion or laboratory proven
  • Previous vaccination against varicella
  • Previous vaccination with JE-CV in JEC02 study
  • History of varicella, confirmed either clinically, serologically, or microbiologically
  • Known systemic hypersensitivity or anaphylactic/anaphylactoid reaction to neomycin.
  • Known history of thrombocytopenia or idiopathic thrombocytopenic purpura

Temporary Contraindications:

A prospective participant was not to be included in the study until the following conditions and/or symptoms had resolved:

  1. Receipt of oral or injected antibiotic therapy within 72 hours prior to the first blood draw (for Groups 1 and 2)
  2. Febrile illness (temperature ≥38.0°C [≥100.4°F]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination (for all participants)

The Investigator was to postpone vaccination until the situation/condition resolved. Vaccination could be postponed within the timeframe for vaccination indicated in the protocol trial flowchart.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Group 1: JE-CV Vaccine Booster

Group 2: JE-CV Vaccine First Dose

Group 3: Varicella Vaccine

Arm Description

Participants previously vaccinated with JE-CV vaccine will receive a booster dose of JE-CV vaccine on Day 0.

JE-CV vaccine naïve participants will receive a single dose of JE-CV vaccine on Day 0.

JE-CV vaccine naïve participants will receive one dose of Varicella vaccine on Day 0.

Outcomes

Primary Outcome Measures

Percentage of Participants With JE Seroprotection Before and Following a Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a 50% plaque reduction neutralization test (PRNT50). Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Day 7 and Day 28) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Percentage of Participants With JE Seroconversion Following a Dose of Live Attenuated JE-CV Vaccine
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroconversion was defined as participants with a pre-vaccination titer <10 (1/dilution) and post-vaccination titer ≥10 (1/dilution, or participants with pre vaccination titer ≥10 (1/dilution) and a ≥4-fold increase from pre- to post-vaccination.
Summary of Geometric Mean Titers of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Summary of Serological Flavivirus Status at Baseline of Participants Vaccinated With a Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Flavivirus positive was defined as titers against JE virus ≥10 (1/dilution) or titers against at least 1 dengue serotype ≥10 (1/dilution). Flavivirus negative was defined as titers against JE virus <10 (1/dilution) and titers against the 4 dengue serotypes <10 (1/dilution).
Percentage of Participants With JE Seroprotection Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Days 7 and 28 and Years 1, 2, 3, 4, and 5) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Summary of Geometric Mean Titer of JE Virus Antibodies Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Number of Participants With Solicited Injection-Site Reactions and Systemic Reactions Following a Dose of Live Attenuated JE-CV or Varicella Vaccine
Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection-site reactions: Pain, Incapacitating, unable to perform usual activities. Erythema and Swelling, ≥5 cm. Grade 3 Systemic reactions: Fever, 39.0°C; Headache, Malaise, and Myalgia, Significant; prevents daily activities.

Secondary Outcome Measures

Full Information

First Posted
August 25, 2010
Last Updated
March 21, 2022
Sponsor
Sanofi Pasteur, a Sanofi Company
search

1. Study Identification

Unique Protocol Identification Number
NCT01190228
Brief Title
Study of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Children Previously Immunized With JE-CV
Official Title
Assessment of the Memory Immune Response, Safety of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Children Previously Immunized With a Single Dose of JE-CV and Long-Term Follow-Up
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
August 25, 2010 (Actual)
Primary Completion Date
October 29, 2010 (Actual)
Study Completion Date
October 12, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of the study is to investigate the memory immune response and the yearly persistence of the immunity against Japanese Encephalitis (JE) after vaccination with Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in participants previously vaccinated with JE-CV vaccine. Objectives: To describe JE immune status before and after JE-CV vaccination in subjects previously vaccinated with JE-CV vaccine To describe the immune status before and after JE-CV vaccination in JE-naïve control subjects. To describe the safety (in terms of solicited and unsolicited adverse events) of a single dose of JE-CV vaccine up to 6 months after the last vaccination. To describe all related serious adverse events (SAEs) and related deaths from 6 months to 5 years after vaccination in JE-CV-primed subjects.
Detailed Description
Study participants who are previously immunized with JE-CV vaccine will receive a booster dose of the JE-CV vaccine and will be followed up for 5 years for immunogenicity. The control (JE-CV naïve) participants will receive either one dose of JE-CV vaccine or one dose of varicella vaccine. All participants will be monitored for safety for 6 month post-vaccination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Japanese Encephalitis, Varicella
Keywords
Japanese Encephalitis, Japanese encephalitis chimeric virus vaccine, Varicella, Varicella vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This was an open, controlled, multicenter, Phase III trial. Participants in Group 1 were previously vaccinated at 12 to 18 months of age with a single dose of JE-CV vaccine and were to receive a booster dose of JE-CV vaccine on Day 0. This group was not randomized. JE vaccine naïve control children were randomized to receive one single dose of JE-CV on Day 0 (Group 2) or a varicella vaccination on Day 0 (Group 3).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
454 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: JE-CV Vaccine Booster
Arm Type
Experimental
Arm Description
Participants previously vaccinated with JE-CV vaccine will receive a booster dose of JE-CV vaccine on Day 0.
Arm Title
Group 2: JE-CV Vaccine First Dose
Arm Type
Experimental
Arm Description
JE-CV vaccine naïve participants will receive a single dose of JE-CV vaccine on Day 0.
Arm Title
Group 3: Varicella Vaccine
Arm Type
Active Comparator
Arm Description
JE-CV vaccine naïve participants will receive one dose of Varicella vaccine on Day 0.
Intervention Type
Biological
Intervention Name(s)
JE-CV Vaccine
Other Intervention Name(s)
IMOJEV
Intervention Description
0.5 mL (single dose), Subcutaneous
Intervention Type
Biological
Intervention Name(s)
Varicella Vaccine
Other Intervention Name(s)
OKAVAX®
Intervention Description
0.5 mL (single dose), Subcutaneous
Primary Outcome Measure Information:
Title
Percentage of Participants With JE Seroprotection Before and Following a Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a 50% plaque reduction neutralization test (PRNT50). Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Day 7 and Day 28) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Time Frame
Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Title
Percentage of Participants With JE Seroconversion Following a Dose of Live Attenuated JE-CV Vaccine
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroconversion was defined as participants with a pre-vaccination titer <10 (1/dilution) and post-vaccination titer ≥10 (1/dilution, or participants with pre vaccination titer ≥10 (1/dilution) and a ≥4-fold increase from pre- to post-vaccination.
Time Frame
Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Title
Summary of Geometric Mean Titers of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame
Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Title
Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame
Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Title
Summary of Serological Flavivirus Status at Baseline of Participants Vaccinated With a Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Flavivirus positive was defined as titers against JE virus ≥10 (1/dilution) or titers against at least 1 dengue serotype ≥10 (1/dilution). Flavivirus negative was defined as titers against JE virus <10 (1/dilution) and titers against the 4 dengue serotypes <10 (1/dilution).
Time Frame
Day 0 (pre-vaccination)
Title
Percentage of Participants With JE Seroprotection Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Days 7 and 28 and Years 1, 2, 3, 4, and 5) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Time Frame
Day 0 (pre-vaccination) and Days 7 and 28, and Year 1, 2, 3, 4, and 5 post-vaccination
Title
Summary of Geometric Mean Titer of JE Virus Antibodies Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame
Day 0 (pre-vaccination) and Days 7 and 28 and Year 1, 2, 3, 4, and 5 post-vaccination
Title
Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Description
The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame
Year 1, 2, 3, 4, and 5 post-vaccination
Title
Number of Participants With Solicited Injection-Site Reactions and Systemic Reactions Following a Dose of Live Attenuated JE-CV or Varicella Vaccine
Description
Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection-site reactions: Pain, Incapacitating, unable to perform usual activities. Erythema and Swelling, ≥5 cm. Grade 3 Systemic reactions: Fever, 39.0°C; Headache, Malaise, and Myalgia, Significant; prevents daily activities.
Time Frame
Day 0 up to Day 14 post-vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
36 Months
Maximum Age & Unit of Time
42 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
An individual had to fulfill all of the following criteria in order to be eligible for trial enrollment: All Participants Aged 36 to 42 months on the day of inclusion Provision of Informed Consent Form signed by at least one parent or other legally acceptable representative Participant and parent/legally acceptable representative or guardian able to attend all scheduled visits and to comply with all trial procedures In good general health, based on medical history and physical examination For JE-CV vaccine primed group only Participant who was vaccinated with JE-CV in JEC02 trial (NCT00735644) An individual fulfilling any of the following criteria was excluded from trial enrollment: All Participants Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial vaccination Planned participation in another clinical trial during the Day 0 - Month 6 period and for Group 1 up to 5 years for any flavivirus vaccine trial Receipt of any vaccine* in the 4 weeks preceding the trial vaccination, except for pandemic influenza vaccination, which may be received at least 2 weeks before study vaccines Planned receipt of any vaccine* in the 4 weeks following the trial vaccination, except for pandemic influenza vaccine. In the event of local or national immunization program with a pandemic influenza vaccine, participants who receive a pandemic influenza vaccine at any time during the trial will not be withdrawn from the trial. Planned receipt of any JE vaccine during the course of the trial Administration of any anti-viral within 2 months preceding the trial vaccination and up to 4 weeks following the trial vaccination Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, as reported by the parent/legally acceptable representative History of central nervous system disorder or disease, including seizures and febrile seizures Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances Chronic illness or any underlying illness (such as cardiovascular, kidney, liver or hematological disease or development abnormalities) that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion Except in case of national immunization days with oral polio vaccine For JE-CV primed participants only Receipt of any JE vaccine other than JE-CV during JEC02 trial(NCT00735644) and since the end of JEC02 trial For JE-CV naïve participants only Previous vaccination against flavivirus disease including JE History of flavivirus infection either based on clinical suspicion or laboratory proven Previous vaccination against varicella Previous vaccination with JE-CV in JEC02 study History of varicella, confirmed either clinically, serologically, or microbiologically Known systemic hypersensitivity or anaphylactic/anaphylactoid reaction to neomycin. Known history of thrombocytopenia or idiopathic thrombocytopenic purpura Temporary Contraindications: A prospective participant was not to be included in the study until the following conditions and/or symptoms had resolved: Receipt of oral or injected antibiotic therapy within 72 hours prior to the first blood draw (for Groups 1 and 2) Febrile illness (temperature ≥38.0°C [≥100.4°F]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination (for all participants) The Investigator was to postpone vaccination until the situation/condition resolved. Vaccination could be postponed within the timeframe for vaccination indicated in the protocol trial flowchart.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur SA
Official's Role
Study Director
Facility Information:
City
Muntinlupa City
ZIP/Postal Code
1781
Country
Philippines

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
29325161
Citation
Capeding MR, Alberto ER, Bouckenooghe A, Laot TM, Chansinghakul D, Monfredo C, Machabert T, Feroldi E. Five-Year Antibody Persistence Following a Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) Booster in JE-CV-Primed Children in the Philippines. J Infect Dis. 2018 Jan 30;217(4):567-571. doi: 10.1093/infdis/jix601.
Results Reference
derived
Links:
URL
http://www.sanofipasteur.com
Description
Related Info

Learn more about this trial

Study of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Children Previously Immunized With JE-CV

We'll reach out to this number within 24 hrs