Encephalitis, Tick-Borne
Conditions
Brief summary
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).
Interventions
Subjects receive three vaccinations with FSME-IMMUN 0.25ml Junior on days 0, 28 and 360
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
1 Years to 11 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seropositivity Rate as Determined by Neutralization Test (NT) 28 Days After the Second Vaccination | 28 days after Vaccination 2 | Percentage of participants achieving NT titer greater than or equal to (\>=) 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 days after Vaccination 2, 180 days after the Vaccination 1, 28 days after the Vaccination 3 | 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. |
| Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3 | Geometric mean of antibody response measured by NT. Here, Number Analyzed signifies number of participants who were evaluable at the specified timeframe. |
| Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3 | 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. |
| 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 | 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3 | 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. |
| 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 | 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3 | 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. |
| Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Within 28 days after Vaccination 1 | 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. |
| Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 days after the Vaccination 1, 28 days after the Vaccination 3 | 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. |
| Frequency and Severity of Systemic Reactions Occurring After Third Vaccination | Within 28 days after Vaccination 3 | 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. |
| Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Within 6 days of Vaccination 1 | 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. |
| Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Within 6 days of Vaccination 2 | 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. |
| Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination | Within 6 days of Vaccination 3 | 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. |
| Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Part A: Within 28 days after Vaccination 1 and Vaccination 2, Part B: 28 days after Vaccination 2 to before Vaccination 3 | 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. |
| Frequency and Severity of Adverse Events (AE) Observed After the Third Vaccination | Within 28 days after Vaccination 3 | 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. |
| Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Within 28 days after Vaccination 2 | 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. |
Countries
Austria, Czechia
Participant flow
Pre-assignment details
The study was conducted from 06 February 2009 to 20 May 2010 in Austria and Czech Republic.
Participants by arm
| Arm | Count |
|---|---|
| Part A: FSME-IMMUN Participants received FSME-IMMUN (FSME-IMMUN Junior) at Day 0 and 28 as first and second vaccination according to the conventional immunization schedule. | 150 |
| Part A: Encepur Participants received Encepur (Encepur Children) at Day 0 and 28 as first and second vaccination according to the conventional immunization schedule. | 152 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A: Screening- Day 28 Postdose 2 | Screen failure | 1 | 0 | 0 |
| Part B:Day 28 Postdose2-Day 28 Postdose3 | Lost to Follow-up | 0 | 0 | 1 |
| Part B:Day 28 Postdose2-Day 28 Postdose3 | Other | 0 | 0 | 1 |
| Part B:Day 28 Postdose2-Day 28 Postdose3 | Refused blood draw | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Part A: FSME-IMMUN | Part A: Encepur | Total |
|---|---|---|---|
| Age, Customized Children (2-11 years) | 100 Participants | 102 Participants | 202 Participants |
| Age, Customized Infants and toddlers (28 days- 23 months) | 50 Participants | 50 Participants | 100 Participants |
| Sex: Female, Male Female | 77 Participants | 74 Participants | 151 Participants |
| Sex: Female, Male Male | 73 Participants | 78 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 50 | 13 / 50 | 37 / 50 | 15 / 51 | 11 / 51 | 30 / 51 | 14 / 49 | 10 / 49 | 30 / 48 | 25 / 50 | 13 / 50 | 39 / 50 | 33 / 51 | 19 / 51 | 33 / 51 | 30 / 51 | 26 / 51 | 30 / 51 | 23 / 99 | 29 / 100 | 30 / 99 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 | 1 / 50 | 0 / 51 | 0 / 51 | 3 / 51 | 0 / 49 | 0 / 49 | 2 / 48 | 0 / 50 | 0 / 50 | 4 / 50 | 0 / 51 | 0 / 51 | 3 / 51 | 0 / 51 | 0 / 51 | 3 / 51 | 0 / 99 | 0 / 100 | 0 / 99 |
Outcome results
Primary
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.
Time frame: 28 days after Vaccination 2
Population: Per-protocol analysis set included eligible participants who received first and second vaccination; had negative baseline values in NT; had immunogenicity measurements available at baseline; 28 days after second vaccination and no major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FSME-IMMUN | Seropositivity Rate as Determined by Neutralization Test (NT) 28 Days After the Second Vaccination | 100 Percentage of participants |
| Encepur | Seropositivity Rate as Determined by Neutralization Test (NT) 28 Days After the Second Vaccination | 97.8 Percentage of participants |
Comparison: Non-inferiority Test on Seropositive Response Ratep-value: <0.001Stratified score test
Secondary
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.
Time frame: 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Population: mITT analysis set included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA (IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA) and NT, had immunogenicity measurements available at baseline and 28 days after the second vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 180 Days after Vaccination 1 | 493.7 titer |
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 28 Days after Vaccination 2 | 3026.3 titer |
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 28 Days after Vaccination 3 | 11292.9 titer |
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 180 Days after Vaccination 1 | 47.9 titer |
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 28 Days after Vaccination 2 | 163.3 titer |
| FSME-IMMUN | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 28 Days after Vaccination 3 | 682.2 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 28 Days after Vaccination 2 | 93.7 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 180 Days after Vaccination 1 | 161.2 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 180 Days after Vaccination 1 | 26.7 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 28 Days after Vaccination 2 | 678 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | Enzygnost: 28 Days after Vaccination 3 | 673.2 titer |
| Encepur | Antibody Response Measured by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | IMMUNOZYM: 28 Days after Vaccination 3 | 10508.6 titer |
Secondary
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.
Time frame: 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Population: mITT analysis set included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA (IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA) and NT, had immunogenicity measurements available at baseline and 28 days after second vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FSME-IMMUN | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 39.7 titer |
| FSME-IMMUN | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 2 | 236.8 titer |
| FSME-IMMUN | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 538.2 titer |
| Encepur | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 25 titer |
| Encepur | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 2 | 118.8 titer |
| Encepur | Antibody Response Measured by NT 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 521.3 titer |
Secondary
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.
Time frame: 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Population: mITT population included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA (IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA) and NT, had immunogenicity measurements available at baseline and 28 days after the second vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FSME-IMMUN | 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 | IMMUNOZYM: 180 Days after Vaccination 1 | 31.6 fold rise |
| FSME-IMMUN | 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 | IMMUNOZYM: 28 Days after Vaccination 2 | 193.7 fold rise |
| FSME-IMMUN | 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 | IMMUNOZYM: 28 Days after Vaccination 3 | 719.9 fold rise |
| FSME-IMMUN | 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 | Enzygnost: 180 Days after Vaccination 1 | 9.5 fold rise |
| FSME-IMMUN | 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 | Enzygnost: 28 Days after Vaccination 2 | 32.5 fold rise |
| FSME-IMMUN | 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 | Enzygnost: 28 Days after Vaccination 3 | 135.8 fold rise |
| Encepur | 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 | Enzygnost: 28 Days after Vaccination 2 | 18.7 fold rise |
| Encepur | 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 | IMMUNOZYM: 180 Days after Vaccination 1 | 9.5 fold rise |
| Encepur | 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 | Enzygnost: 180 Days after Vaccination 1 | 5.3 fold rise |
| Encepur | 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 | IMMUNOZYM: 28 Days after Vaccination 2 | 39.9 fold rise |
| Encepur | 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 | Enzygnost: 28 Days after Vaccination 3 | 134.6 fold rise |
| Encepur | 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 | IMMUNOZYM: 28 Days after Vaccination 3 | 620.9 fold rise |
Secondary
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.
Time frame: 28 days after Vaccination 2, 180 days after Vaccination 1, 28 days after Vaccination 3
Population: mITT analysis set included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA (IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA) and NT, had immunogenicity measurements available at baseline and 28 days after second vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FSME-IMMUN | 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 | 180 Days after Vaccination 1 | 7.9 fold rise |
| FSME-IMMUN | 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 | 28 Days after Vaccination 2 | 46.9 fold rise |
| FSME-IMMUN | 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 | 28 Days after Vaccination 3 | 106.7 fold rise |
| Encepur | 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 | 180 Days after Vaccination 1 | 5 fold rise |
| Encepur | 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 | 28 Days after Vaccination 2 | 23.6 fold rise |
| Encepur | 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 | 28 Days after Vaccination 3 | 103.5 fold rise |
Secondary
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.
Time frame: Within 28 days after Vaccination 3
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed After the Third Vaccination | Non-Serious AE: within 28 days after Vaccination 3 | 102 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed After the Third Vaccination | Serious AE: within 28 days after Vaccination 3 | 0 participants |
Secondary
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.
Time frame: Part A: Within 28 days after Vaccination 1 and Vaccination 2, Part B: 28 days after Vaccination 2 to before Vaccination 3
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE: within 28 days after Vaccination 1 | 57 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: within 28 days after Vaccination 1 | 1 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE: within 28 days after Vaccination 2 | 42 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: within 28 days after Vaccination 2 | 0 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE:after Part A to before Vaccination3 | 97 participants |
| FSME-IMMUN | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: after Part A to before Vaccination 3 | 6 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE:after Part A to before Vaccination3 | 102 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE: within 28 days after Vaccination 1 | 80 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: within 28 days after Vaccination 2 | 0 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: within 28 days after Vaccination 1 | 0 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Serious AE: after Part A to before Vaccination 3 | 10 participants |
| Encepur | Frequency and Severity of Adverse Events (AE) Observed Before the Third Vaccination | Non-Serious AE: within 28 days after Vaccination 2 | 66 participants |
Secondary
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.
Time frame: Within 6 days of Vaccination 1
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Severe | 0 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | None | 131 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Unknown | 1 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Mild | 18 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Moderate | 0 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Moderate | 3 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Mild | 41 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | None | 108 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Severe | 0 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the First Vaccination | Unknown | 0 participants |
Secondary
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.
Time frame: Within 6 days of Vaccination 2
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | None | 137 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Mild | 12 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Moderate | 1 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Severe | 0 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Severe | 0 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | None | 118 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Moderate | 7 participants |
| Encepur | Frequency and Severity of Injection Site Reactions Occurring After the Second Vaccination | Mild | 27 participants |
Secondary
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.
Time frame: Within 6 days of Vaccination 3
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination | None | 249 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination | Mild | 43 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination | Moderate | 4 participants |
| FSME-IMMUN | Frequency and Severity of Injection Site Reactions Occurring After the Third Vaccination | Severe | 2 participants |
Secondary
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.
Time frame: Within 28 days after Vaccination 1
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: None | 136 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Mild | 13 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Moderate | 1 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Severe | 0 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Severe | 0 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: None | 134 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Moderate | 3 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After First Vaccination | Systemic reactions: Mild | 15 participants |
Secondary
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.
Time frame: Within 28 days after Vaccination 2
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: None | 143 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Mild | 7 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Moderate | 0 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Severe | 0 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Severe | 0 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: None | 144 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Moderate | 0 participants |
| Encepur | Frequency and Severity of Systemic Reactions Occurring After Second Vaccination | Systemic reactions: Mild | 8 participants |
Secondary
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.
Time frame: Within 28 days after Vaccination 3
Population: The safety analysis set included all participants who received the third vaccination of FSME-IMMUN, after first 2 doses of FSME-IMMUN or Encepur and had documented adverse event information at least immediately afterwards.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Third Vaccination | Systemic reactions: None | 282 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Third Vaccination | Systemic reactions: Mild | 15 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Third Vaccination | Systemic reactions: Moderate | 1 participants |
| FSME-IMMUN | Frequency and Severity of Systemic Reactions Occurring After Third Vaccination | Systemic reactions: Severe | 0 participants |
Secondary
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.
Time frame: 28 days after Vaccination 2, 180 days after the Vaccination 1, 28 days after the Vaccination 3
Population: mITT analysis set included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA (IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA) and NT, had immunogenicity measurements available at baseline and 28 days after second vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 95.1 percentage of participants |
| FSME-IMMUN | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 2 | 100 percentage of participants |
| FSME-IMMUN | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 100 percentage of participants |
| Encepur | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 81.5 percentage of participants |
| Encepur | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 2 | 97.3 percentage of participants |
| Encepur | Seropositivity Rate Determined by ELISA 28 Days After the Second Vaccination, 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 100 percentage of participants |
Secondary
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.
Time frame: 180 days after the Vaccination 1, 28 days after the Vaccination 3
Population: mITT analysis set included eligible participants who fulfilled all inclusion and exclusion criteria, received first and second vaccination, had no positive baseline values in ELISA(IMMUNOZYM FSME ELISA and Enzygnost TBE ELISA)and NT, had immunogenicity measurements available at baseline and 28 days after second vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSME-IMMUN | Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 95.3 Percentage of participants |
| FSME-IMMUN | Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 100 Percentage of participants |
| Encepur | Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 180 Days after Vaccination 1 | 91 Percentage of participants |
| Encepur | Seropositivity Rate Determined by NT 180 Days After the First Vaccination and 28 Days After the Third Vaccination | 28 Days after Vaccination 3 | 100 Percentage of participants |