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

• ClinicalTrials.gov Identifier: NCT01190228
• Recruitment Status: Completed
• First Posted: August 27, 2010
• Results First Posted: November 8, 2017
• Last Update Posted: November 8, 2017
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

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.

Condition or disease	Intervention/treatment	Phase
Japanese Encephalitis; Varicella	Biological: JE-CV Vaccine; Biological: Varicella Vaccine	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 454 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: August 25, 2010
• Actual Primary Completion Date: October 29, 2010
• Actual Study Completion Date: October 12, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1: JE-CV Vaccine Booster; Participants previously vaccinated with JE-CV vaccine will receive a booster dose of JE-CV vaccine on Day 0.	Biological: JE-CV Vaccine; 0.5 mL (single dose), Subcutaneous; Other Name: IMOJEV
Experimental: Group 2: JE-CV Vaccine First Dose; JE-CV vaccine naïve participants will receive a single dose of JE-CV vaccine on Day 0.	Biological: JE-CV Vaccine; 0.5 mL (single dose), Subcutaneous; Other Name: IMOJEV
Active Comparator: Group 3: Varicella Vaccine; JE-CV vaccine naïve participants will receive one dose of Varicella vaccine on Day 0.	Biological: Varicella Vaccine; 0.5 mL (single dose), Subcutaneous; Other Name: OKAVAX®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With JE Seroprotection Before and Following a Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination ]
   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).
2. Percentage of Participants With JE Seroconversion Following a Dose of Live Attenuated JE-CV Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination ]
   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.
3. Summary of Geometric Mean Titers of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination ]
   The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
4. Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination ]
   The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
5. Summary of Serological Flavivirus Status at Baseline of Participants Vaccinated With a Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) ]
   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).
6. Percentage of Participants With JE Seroprotection Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) and Days 7 and 28, and Year 1, 2, 3, 4, and 5 post-vaccination ]
   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).
7. Summary of Geometric Mean Titer of JE Virus Antibodies Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV [ Time Frame: Day 0 (pre-vaccination) and Days 7 and 28 and Year 1, 2, 3, 4, and 5 post-vaccination ]
   The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
8. Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV [ Time Frame: Year 1, 2, 3, 4, and 5 post-vaccination ]
   The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
9. Number of Participants With Solicited Injection-Site Reactions and Systemic Reactions Following a Dose of Live Attenuated JE-CV or Varicella Vaccine [ Time Frame: Day 0 up to Day 14 post-vaccination ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 36 Months to 42 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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:

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.

Contacts and Locations

Locations

Philippines

Muntinlupa City, Philippines, 1781

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur SA

More Information

Additional Information:

Related Info 

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01190228
• Other Study ID Numbers: JEC15; UTN: U1111-1113-3629 ( Other Identifier: WHO )
• First Posted: August 27, 2010
• Results First Posted: November 8, 2017
• Last Update Posted: November 8, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at www.clinicalstudydatarequest.com. While making information available, Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: Clinicalstudydatarequest.com.

• 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

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Japanese Encephalitis; Japanese encephalitis chimeric virus vaccine; Varicella; Varicella vaccine

Additional relevant MeSH terms:

Chickenpox; Herpes Zoster; Encephalitis, Japanese; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Encephalitis, Arbovirus; Arbovirus Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Infectious Encephalitis; Central Nervous System Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs