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Safety and Immunogenicity of the Japanese Encephalitis Vaccine IC51 (IXIARO®) in a Pediatric Population

Phase 3
Completed
Conditions
Encephalitis
Interventions
Biological: IC51 Japanese Encephalitis
Biological: Havrix®720
Biological: Prevnar
Registration Number
NCT01041573
Lead Sponsor
Valneva Austria GmbH
Brief Summary

The primary objective is to assess the systemic and local safety profile of purified inactivated Japanese Encephalitis Virus (JEV) vaccine IC51 administered in two doses in a 28 days interval up to Month 7 after the first IC51 vaccination in a pediatric population from endemic regions.

Detailed Description

Open-label, randomized, active controlled Phase 3 study in children aged ≥ 2 months to \< 18 years. Subjects aged ≥ 2 months to \< 12 months were randomized in a 2:1 ratio to receive IC51 (0.25 ml dose) or Prevnar® as a safety comparator. Children aged ≥ 12 months to \< 3 years and ≥ 12 years to \< 18 years were randomized in a 3:1 ratio to receive IC51 (0.25 ml dose \< 3 years, 0.5 ml ≥ 12 years) or HAVRIX®720 as safety comparator.

For subjects aged ≥ 3 years to \< 12 years, a dose finding run-in phase was performed. A total of 200 subjects were randomized 1:1 to receive either the 0.25 ml or the 0.5 ml dose of IC51, and the appropriate dose was determined based on an interim analysis. After this run-in phase, 300 further children in this age group were randomized 2:1 to receive either 0.5 ml of IC51 or HAVRIX®720.

Immunogenicity was be studied in a subgroup of 30 children aged ≥ 2 months to \< 12 months; 125 children aged ≥ 12 months to \< 3 years and 140 children ≥ 12 years to \< 18 years. For the age group of ≥ 3 to \< 12 years immunogenicity was assessed in the 200 children enrolled during the dose-finding run-in phase.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1869
Inclusion Criteria
  • Male or female healthy children and adolescents aged > 2 months to < 18 years at the time of first vaccination.
  • 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, for females after menarche willingness to practice a reliable method of contraception.
Exclusion Criteria
  • Clinical manifestation of Japanese Encephalitis
  • History of Flavivirus vaccination (including any investigational vaccines)
  • History of vaccination with HAVRIX®720 and/or Prevnar®
  • History of immunodeficiency or immunosuppressive therapy
  • Known HIV, HBV or HCV infection
  • History of hypersensitivity reactions to other vaccines
  • Acute febrile infection at each visit during which the subject receives a vaccination
  • Active or passive immunization within 2 weeks prior to the first IC51 vaccination and up to the second IC51 vaccination.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IC51 0.5 mLIC51 Japanese EncephalitisJapanese Encephalitis Vaccine 6mcg im. at day 0 and day 28
IC51 0.25 mLIC51 Japanese EncephalitisJapanese Encephalitis Vaccine 3mcg im. at day 0 and day 28
Havrix 720Havrix®720Havrix®720 0.5 ml im. at day 0 and month 7
PrevnarPrevnarPrevnar 0.5 ml im. at day 0 and day 56 and month 7 or 0.5 ml im. at day 0, day 28 and day56 and month 7-13
Primary Outcome Measures
NameTimeMethod
Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccinationuntil Day 56

Rate of subjects with these types of AEs, comparison vs respective control vaccine stratified by age group: All study participants aged \< 1 year: IC51 0.25mL vs. Prevnar; All study participants aged 1 year and above: IC51 0.25 mL or =.5 mL vs. Havrix.

Secondary Outcome Measures
NameTimeMethod
Geometric Mean Titers (GMT) for JEV Neutralizing AntibodiesDay 0, 56 and at Month 7

GMT for JEV neutralizing antibodies is presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years.

Rate of Subjects With Solicited Local and Systemic AEs7 days post vaccination

Rate of subjects with solicited local and systemic AEs. Solicited AEs of local and systemic tolerability, i.e., reactions at the injection site or systemic reactions typical for vaccinations, were to be evaluated for 7 consecutive days after each vaccination (except after the HAVRIX®750 and Prevnar® injections at Month 7 \[Visit 4\]) and recorded in the subject diary.

For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.

Rate of Subjects With Abnormal Laboratory ParametersDay 56 and Month 7

Rate of subjects with abnormal laboratory parameters clinically significant results are shown below

Seroconversion Rate (SCR) at Days 0, 56 and at Month 7Days 0, 56 and at Month 7

Seroconversion was defined as a PRNT50 titer of at least 1:10. SCRs are presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years.

Rate of Subjects With SAEs and Medically Attended AEsup to Month 7

Rate of subjects with SAEs and medically attended AEs; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.

Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7Day 56 and up to Month 7

Rate of subjects with unsolicited AEs up to Day 56 and up to Month 7; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.

Trial Locations

Locations (2)

Research Institute for Tropical Medicine

🇵🇭

Muntinlupa, Filinvest Corporate City, Philippines

Department of Pediatrics, UP-Philippine General Hospital

🇵🇭

Manila, Philippines

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