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

Encephalitis Clinical Trial

Official title:

Safety and Immunogenicity of the Japanese Encephalitis Vaccine IC51 (IXIARO®) in a Pediatric Population. Open Label, Randomized, Active Controlled, Phase 3 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01041573
• Other study ID #: IC51-323
• Status: Completed
• Phase: Phase 3
• Start date: March 2010
• Est. completion date: July 2011

Study information

• Verified date: July 2021
• Source: Valneva Austria GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1869
• Est. completion date: July 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese

Intervention

Biological:
• IC51 Japanese Encephalitis
6 mcg or 3 mcg im. at day 0 and day 28
• Havrix®720
0.5 ml im. at day 0 and month 7
• Prevnar
0.5 ml im. at day 0 and day 56 and month 7

Locations

Country	Name	City	State
Philippines	Department of Pediatrics, UP-Philippine General Hospital	Manila
Philippines	Research Institute for Tropical Medicine	Muntinlupa	Filinvest Corporate City

Sponsors (1)

Lead Sponsor	Collaborator
Valneva Austria GmbH

Country where clinical trial is conducted

Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination	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.	until Day 56
Secondary	Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies	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.	Day 0, 56 and at Month 7
Secondary	Seroconversion Rate (SCR) at Days 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.	Days 0, 56 and at Month 7
Secondary	Rate of Subjects With SAEs and Medically Attended AEs	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.	up to Month 7
Secondary	Rate of Subjects With Solicited Local and Systemic AEs	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.	7 days post vaccination
Secondary	Rate of Subjects With Unsolicited AEs up to Day 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.	Day 56 and up to Month 7
Secondary	Rate of Subjects With Abnormal Laboratory Parameters	Rate of subjects with abnormal laboratory parameters clinically significant results are shown below	Day 56 and Month 7