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

NCT01190228 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: JEC15UTN: U1111-1113-3629
• Study Type: interventional
• Target: 454
• Locations: 1 country
• Sites: 1

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.

Conditions

Japanese Encephalitis; Varicella

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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).

  Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination

• 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.

  Day 0 (pre-vaccination) and Day 7 and Day 28 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.

  Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination

• 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.

  Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination

• 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).

  Day 0 (pre-vaccination)

• 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).

  Day 0 (pre-vaccination) and Days 7 and 28, and Year 1, 2, 3, 4, and 5 post-vaccination

• 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.

  Day 0 (pre-vaccination) and Days 7 and 28 and Year 1, 2, 3, 4, and 5 post-vaccination

• 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.

  Year 1, 2, 3, 4, and 5 post-vaccination

• 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.

  Day 0 up to Day 14 post-vaccination

Study Arms (3)

Group 1: JE-CV Vaccine Booster

EXPERIMENTAL

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

Biological: JE-CV Vaccine

Group 2: JE-CV Vaccine First Dose

EXPERIMENTAL

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

Biological: JE-CV Vaccine

Group 3: Varicella Vaccine

ACTIVE COMPARATOR

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

Biological: Varicella Vaccine

Interventions

JE-CV Vaccine BIOLOGICAL

0.5 mL (single dose), Subcutaneous

Also known as: IMOJEV

Group 1: JE-CV Vaccine Booster; Group 2: JE-CV Vaccine First Dose

Varicella Vaccine BIOLOGICAL

0.5 mL (single dose), Subcutaneous

Also known as: OKAVAX®

Group 3: Varicella Vaccine

Eligibility Criteria

• Age: 36 Months - 42 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Unknown Facility

City of Muntinlupa, 1781, Philippines

Location

Related Publications (1)

• 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.

  PMID: 29325161 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Encephalitis, Japanese; Chickenpox

Interventions

Chickenpox Vaccine

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; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Herpesvirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur Inc.

RegistryContactUs@sanofipasteur.com

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 27, 2010
• Study Start: August 25, 2010
• Primary Completion: October 29, 2010
• Study Completion: October 12, 2015
• Last Updated: March 28, 2022
• Results First Posted: November 8, 2017

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

PH (1)