Open-label, Randomized Study in a Pediatric Population in a JEV (Japanese Encephalitis Virus)-Endemic Country

Long-Term Immunity and Safety With or Without a Booster Dose Following Primary Vaccination With the Japanese Encephalitis Vaccine IC51 (IXIARO®) in a Pediatric Population in a JEV-Endemic Country. Open-Label, Randomized, Phase 3 Study

This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in study IC51-323.

Study Overview

• Status: Completed
• Conditions: Japanese Encephalitis
• Intervention / Treatment: Biological: IXIARO; Biological: IXIARO

Detailed Description

This is a randomized, open-label Phase 3 study including children aged >9 months to <17 years and 7 months who have been vaccinated with IXIARO in the previous study IC51-323.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Philippines
  • Manila, Philippines, 1000
    • UP-Philippine General Hospital
  • Alabang
    • Muntinlupa City, Alabang, Philippines, 1781
      • Research Institute for Tropical Medicine - Clinical Research Division
    • Muntinlupa City, Alabang, Philippines, 1781
      • Research Institute for Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adolescents who have completed study IC51-323 and received both IXIARO vaccinations according to protocol.
• Children who have received the dose confirmed for their age group.
• Male or female healthy children and adolescents aged ≥9 months to <17 years and 7 months at the time of enrolment into this study.
• Written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable.
• Female subjects: either no childbearing potential or negative pregnancy test (pregnancy test to be performed in female subjects after onset of menarche) at Visits 1, 2 and 2a as stipulated by the protocol. For females after menarche willingness to practice a reliable method of contraception

Exclusion Criteria:

• Vaccination against JE virus (JEV) (except within study IC51-323 and IC51 325), Yellow fever, West Nile virus and Dengue fever at any time prior to or planned during the study.
• History of or clinical manifestation of any Flavivirus disease during IC51-323 or IC51 325.
• Participation in another study with an investigational drug during IC51 323 or IC51 325.
• Planned active or passive immunization within 2 weeks before and 1 week after the IXIARO booster.
• History of or development of any immunodeficiency including post-organ-transplantation after inclusion into IC51-323 or IC51 325.

• History of or development of an autoimmune disease during study IC51-323 or IC51 325.

  • Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying medications started during IC51-323 or IC51 325. (For corticosteroids, this would mean prednisone or equivalent at >0.05 mg/kg/day; topical and inhaled steroids are allowed).
• Acute febrile infection at Visit 2 (only for the Booster Group).
• Pregnancy (positive pregnancy test at Visit 1 and Visit 2), lactation or unreliable contraception in female subjects after onset of menarche.
• Hypersensitivity reactions to IXIARO or adverse events in study IC51-323 requiring withdrawal from further vaccination or anaphylaxis or severe cases of atopy requiring emergency treatment or hospital admission during IC51-323 or IC51 325.
• History of urticaria after hymenoptera envenomation, drugs, physical or other provocations or of idiopathic cause during IC51-323 or IC51 325.
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) (measurement of Hepatitis B surface antigen [HBsAg] titers) or hepatitis C virus (HCV).
• Illicit drug use and/or current drug or alcohol addiction.
• Inability or unwillingness by the legal representative(s) and/or the subject (where applicable) to provide informed consent/assent and to abide by the requirements of the study.
• Persons who have been committed to an institution (by a court or by an authority).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: >14 months to <2 years; IXIARO 0.25 ml i.m. (milliliter, intramuscular)	Biological: IXIARO; 0.25 ml i.m. (milliliter, intramuscular); Biological: IXIARO; 0.5 ml i.m. (milliliter, intramuscular)
Active Comparator: >3 years - <18 years; IXIARO 0.5 ml i.m (milliliter, intramuscular)	Biological: IXIARO; 0.25 ml i.m. (milliliter, intramuscular); Biological: IXIARO; 0.5 ml i.m. (milliliter, intramuscular)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
SCRs (Seroconversion Rate) as Defined by Percentage of Subjects With Plaque Reduction Neutralization Test Titers of>1:10 at 1 Month After the Booster Dose	1 month post booster

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of Subjects Achieving a >4-fold Increase in JEV (Japanese Encephalitis Virus) Neutralizing Antibody Titers at 1 Month After the Booster Dose	1 month
GMTs (Geometric Mean Titre) for JEV Neutralizing Antibodies Measured Using a Validated PRNT (Plaque Reduction Neutralization Test) at 1 Month After the Booster Dose	1 month
GMTs and Rate of Subjects With a PRNT Titer of >1:10 at Months 12, 24 and 36 After First IXIARO Vaccination in IC51-323 With and Without Booster Vaccination	36 months
Rate of Subjects With SAEs (Serious Adverse Events) Following Immunization and Medically Attended AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and	36 months
Rate of Subjects With Unsolicited AEs (Adverse Events) up to Months 12, 24 and 36 After the First IXIARO Vaccination in IC51 323 With and Without Booster Vaccination. Severity, Duration and Relationship to Vaccinations.	36 months
Rate of Subjects With SAEs and Medically Attended AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations.	1 month
Rate of Subjects With Unsolicited AEs Within 1 Month Following the Booster Dose. Severity, Duration and Relationship to Vaccinations.	1 month
Rate of Subjects With Solicited AEs for up to 7 Days Following the Booster Dose. Severity and Duration.	7 days

Collaborators and Investigators

• Sponsor: Valneva Austria GmbH
• Investigators: Study Chair: Vera Kadlecek, Mag., Valneva Austria GmbH

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 28, 2010
• First Submitted That Met QC Criteria: February 14, 2011
• First Posted (Estimate): February 15, 2011

Study Record Updates

• Last Update Posted (Estimate): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 10, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: immune response; Japanese Encephalitis; IC51-325; Intercell AG
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Encephalitis, Japanese; Encephalitis
• Other Study ID Numbers: IC51-325