Immunogenicity, Safety and Interchangeability of Two Tbe Vaccines Administered According to a Conventional Schedule in Children

SINGLE-BLIND, RANDOMIZED, PHASE III B STUDY IN CHILDREN AGED 1 - 11 YEARS TO INVESTIGATE THE IMMUNOGENICITY, SAFETY AND INTERCHANGEABILITY OF TWO TICK-BORNE ENCEPHALITIS (TBE) VACCINES ADMINISTERED ACCORDING TO A CONVENTIONAL SCHEDULE

The objective of this study is to assess the immunogenicity, safety and interchangeability of two different TBE vaccines in children aged 1-11 years, the first and second vaccination with either FSME-IMMUN 0.25ml Junior or Encepur 0.25ml Children and the third vaccination with FSME-IMMUN 0.25 ml Junior only, administered according to the conventional schedule (0, 28 and 360 days).

Study Overview

• Status: Completed
• Conditions: Encephalitis, Tick-Borne
• Intervention / Treatment: Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated); Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated)

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Upper Austria
    • Eferding, Upper Austria, Austria, 4070
      • Unterer Graben 2
    • Wels, Upper Austria, Austria, 4600
      • Grieskirchnerstr.17
• Czechia
  • Havlickuv Brod, Czechia, 580 01
    • Private surgery of General Practitioner for children and juveniles
  • Hradec Králové, Czechia, 50005
    • University Hospital Hradec Kralove, Vaccinal center, Clinic of infectious diseases, Sokolská 581
  • Pardubice, Czechia, 530 02
    • Private surgery of General Practitioner for children and juveniles
  • Pardubice, Czechia, 530 03
    • Private surgery of General Practitioner for children and juveniles
  • Pardubice, Czechia, 530 09
    • Private surgery of General Practitioner for children and juveniles
  • Pardubice-Polabiny, Czechia, 530 09
    • Chemiku 129

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 9 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Male and female children will be eligible for participation in this study if:

• they are aged >= 1 years (from the 1st birthday) to 11 years (to the last day before the 12th birthday) at screening;
• their parents / legal guardians provide written informed consent;
• children provide written assent to the study according to age and capacity of understanding;
• their parents/guardians understand the nature of the clinical study and will comply with the requirements of the protocol (e.g., completion of the Subject Diary, return for follow-up visits);
• they are generally healthy, (i.e. the physician would have no reservations vaccinating with a TBE vaccine outside the scope of a clinical study);
• provide a negative pregnancy test result at the first medical examination (if the subject is a female and capable of bearing children).

Exclusion Criteria:

Subjects will be excluded from participation if:

• they have a history of any previous TBE vaccination;
• they have a history of TBE infection;
• they have a history of infection with other flaviviruses;
• they have a history of vaccination against yellow fever and/or Japanese B encephalitis;
• they have a history of severe allergic reactions, in particular a known sensitivity or allergy to any components of the vaccines;
• they are suffering from a disease (e.g. autoimmune disease) or are undergoing a form of treatment (e.g. systemic corticosteroids) that can be expected to influence immunological functions;
• they have received any blood product or immunoglobulins within 90 days prior to study entry;
• they are known to be Human Immunodeficiency Virus (HIV) positive (an HIV test is not required specifically for the purpose of this study);
• they have a functional or surgical asplenia;
• they have a rash or other dermatological condition at the injection site which could interfere with injection site reaction evaluation;
• they were administered an investigational product within six weeks prior to study start or are concurrently participating in another clinical study that includes the administration of an investigational product;
• they are pregnant or breastfeeding (if a female subject);
• they or their parents/legal guardian(s) are in a dependent relationship with the study investigator or with a study team member. Dependent relationship includes close relatives (i.e., children or grandchildren, partner/spouse, siblings) as well as employees of the investigator or site conducting the study.
• Subjects who have an acute illness with or without elevated body temperature (>=37.5°C) within 3 days prior to the scheduled first vaccination will not be vaccinated. Subjects may be included at a repeat visit provided that (1) the illness has resolved (body temperature < 37.5 °C), (2) the repeat visit is no more than 14 calendar days after the Screening Visit, and (3) the center is still open for recruitment.
• If subjects have received antipyretics within 4 hours prior to the scheduled time of vaccination, the vaccination should be performed at a later date, as long as the center is still open for recruitment.
• Subjects who received any live vaccine within 4 weeks or any inactivated vaccine within 2 weeks prior to the scheduled first study vaccination will not be vaccinated until an interval of 4 or 2 weeks, respectively, has passed, provided the center is still open for recruitment.
• If a subject was bitten by a tick within 4 weeks prior to the scheduled first or second vaccination, the vaccination must be postponed until an interval of 4 weeks has passed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Subjects receive three vaccinations with a paediatric TBE vaccine according to the conventional vaccination schedule.	Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated); Subjects receive three vaccinations with FSME-IMMUN 0.25ml Junior on days 0, 28 and 360; Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated); Subjects receive two vaccinations with Encepur 0.25ml Children on days 0 and 28 and a third vaccination with FSME-IMMUN 0.25ml Junior on day 360.
Experimental: 2; Subjects receive three vaccinations with a paediatric TBE vaccine according to the conventional vaccination schedule.	Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated); Subjects receive three vaccinations with FSME-IMMUN 0.25ml Junior on days 0, 28 and 360; Biological: Tick-Borne Encephalitis (TBE) Vaccine (Inactivated); Subjects receive two vaccinations with Encepur 0.25ml Children on days 0 and 28 and a third vaccination with FSME-IMMUN 0.25ml Junior on day 360.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seropositivity Rate as Determined by Neutralization Test (NT) 28 Days After the Second Vaccination	Percentage of participants achieving NT titer greater than or equal to (>=) 10.	28 days after Vaccination 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination	Percentage of participants with NT titer >=10. Here, "number of participants analyzed" signifies total number of participants included in the modified intent-to-treat (mITT) population and "Number Analyzed" signifies number of participants who were evaluable at specified timeframe.	180 days after the Vaccination 1, 28 days after the Vaccination 3
Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination	Percentage of participants with IMMUNOZYM ELISA >126 Vienna Units per milliliter (VIEU/mL) or Enzygnost ELISA >10.32 Units per milliliter (U/mL). Here, "Number Analyzed" signifies number of participants who were evaluable at the specified timeframe.	28 days after Vaccination 2, 180 days after the Vaccination 1, 28 days after the Vaccination 3
Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination	Geometric mean of antibody response measured by NT. Here, "Number Analyzed" signifies number of participants who were evaluable at the specified timeframe.	28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination	Geometric mean of antibody response measured by IMMUNOZYM ELISA (VIEU/mL) and Enzygnost ELISA (U/mL). Here, "Number Analyzed" signifies number of participants who were evaluable at specified timeframe for the specified ELISA assay.	28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Fold Increase of Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination as Compared to Baseline	Geometric mean of fold increase of antibody response measured by NT from day 0 to specified timeframe. Here, "Number Analyzed" signifies number of participants who were evaluable at specified timeframe.	28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Fold Increase of Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination as Compared to Baseline	Geometric mean of fold increase of antibody response measured by IMMUNOZYM ELISA (VIEU/ml) and Enzygnost ELISA (U/ml) from day 0 to specified timeframe. Here, "Number Analyzed" signifies number of participants who were evaluable at the specified timeframe for the specified ELISA assay.	28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Frequency and Severity of Systemic Reactions Occurring After First Vaccination	Systemic symptoms included headache, nausea, vomiting, muscle pain, joint pain, swelling of the lymph nodes, loss of appetite and changes in sleeping behavior in all age strata; restlessness in children 1 to 2 years of age; malaise and fatigue in participants 3 to 11 years of age as collected in participant diary. Number of participants with systemic reactions according to severity after first vaccination were reported.	Within 28 days after Vaccination 1
Frequency and Severity of Systemic Reactions Occurring After Second Vaccination	Systemic symptoms included headache, nausea, vomiting, muscle pain, joint pain, swelling of the lymph nodes, loss of appetite and changes in sleeping behavior in all age strata; restlessness in children 1 to 2 years of age; malaise and fatigue in participants 3 to 11 years of age as collected in participant diary. Number of participants with systemic reactions according to severity after second vaccination were reported.	Within 28 days after Vaccination 2
Frequency and Severity of Systemic Reactions Occurring After Third Vaccination	Systemic symptoms included headache, nausea, vomiting, muscle pain, joint pain, swelling of the lymph nodes, loss of appetite and changes in sleeping behavior in all age strata; restlessness in children 1 to 2 years of age; malaise and fatigue in participants 3 to 11 years of age as collected in participant diary. Number of participants with systemic reactions according to severity after third vaccination were reported. Here, "number of participants analyzed" signifies those participants who received FSME-IMMUN or Encepur during the first and second vaccination and received FSME-IMMUN at Day 360 as third vaccination.	Within 28 days after Vaccination 3
Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination	Injection site reactions included swelling, induration, redness, injection site pain and tenderness, ecchymosis and hematoma as collected in participant diary. Number of participants with injection site reactions according to severity after first vaccination were reported.	Within 6 days of Vaccination 1
Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination	Injection site reactions included swelling, induration, redness, injection site pain and tenderness, ecchymosis and hematoma as collected in participant diary. Number of participants with injection site reactions according to severity after second vaccination were reported.	Within 6 days of Vaccination 2
Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination	Injection site reactions included swelling, induration, redness, injection site pain and tenderness, ecchymosis and hematoma as collected in participant diary. Number of participants with injection site reactions according to severity after third vaccination were reported. Here, "number of participants analyzed" signifies those participants who received FSME-IMMUN or Encepur during the first and second vaccination and received FSME-IMMUN at Day 360 as third vaccination.	Within 6 days of Vaccination 3
Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination	An AE was any untoward medical occurrence in a participants who received study vaccination without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study vaccine and up to one month after last dose that were absent before treatment or that worsened relative to pre-treatment state. Number of participants with serious and non-serious adverse events according to severity before third vaccination were reported.	Part A: Within 28 days after Vaccination 1 and Vaccination 2, Part B: 28 days after Vaccination 2 to before Vaccination 3
Frequency and Severity of Adverse Events (AE) Observed After the Third Vaccination	An AE was any untoward medical occurrence in a participants who received study vaccination without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability / incapacity; congenital anomaly. Treatment-emergent are events between first dose of study vaccine and up to one month after last dose that were absent before treatment or that worsened relative to pre-treatment state. Number of participants with serious and non-serious adverse events according to severity after third vaccination were reported. Here, "number of participants analyzed" signifies those participants who received FSME-IMMUN or Encepur during the first and second vaccination and received FSME-IMMUN at Day 360 as third vaccination.	Within 28 days after Vaccination 3

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer; Principal Investigator: Baxter Bioscience Investigator, Baxter BioScience

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2009
• Primary Completion (Actual): May 20, 2010
• Study Completion (Actual): May 20, 2010

Study Registration Dates

• First Submitted: February 9, 2009
• First Submitted That Met QC Criteria: February 9, 2009
• First Posted (Estimated): February 10, 2009

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• 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; Tick-Borne Diseases; Neuroinflammatory Diseases; Encephalitis; Encephalitis, Tick-Borne; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 700801; EUDRACT NUMBER: 2008-002691-10; B9371022 (Other Identifier: Alias Study Number); 2008-002691-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.