Tick-Borne Encephalitis (TBE) Seropersistence After First Booster and Response to a Second Booster in Children, Adolescents and Young Adults (Follow-Up to Study 700401)

Study Overview
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Brief Summary
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The main purpose of this study is to assess the seropersistence of TBE virus antibodies in children, adolescents and young adults who received the first booster vaccination with either FSME-IMMUN 0.25 mL Junior or FSME-IMMUN 0.5 mL in precursor Study 700401.

Official Title
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Open-label Phase Iv Study To Investigate The Seropersistence Of Tick-borne Encephalitis (Tbe) Virus Antibodies After The First Booster And The Response To A Second Booster Vaccination With Fsme-immun In Children, Adolescents And Young Adults (Follow-up To Study 700401)

Conditions
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Encephalitis, Tick-Borne

Intervention / Treatment
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* Biological: FSME-IMMUN 0.25 mL Junior (1.2 µg TBE antigen/0.25 mL) or FSME-IMMUN 0.5 mL (2.4µg TBE antigen/0.5 mL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who participated in precursor Study 700401 and meet ALL of the following criteria are eligible for participation in this study: Subject / parent(s) / legal guardian(s) provide(s) written informed consent (according to national law); Subject provides written assent to the study according to age and capacity of understanding; Subject received the first booster vaccination with either FSME-IMMUN 0.25 ml Junior or FSME-IMMUN 0.5 ml during the course of precursor Study 700401; Blood was drawn after the first booster vaccination in precursor Study 700401; Subject / parent(s) / legal guardian(s) understand(s) the nature of the study and is / are willing to comply with the requirements of the protocol (e.g. return for follow-up visits, completion of the Subject Diary). Exclusion Criteria: Subjects who participated in precursor Study 700401 and meet ANY of the following criteria are not eligible for participation in this study: Subject received any TBE vaccination since his / her first booster vaccination in precursor Study 700401; Subject has a history of infection with or vaccination against other flaviviruses (e.g. Dengue fever, yellow fever, Japanese B encephalitis) since his / her first booster vaccination in precursor Study 700401; Subject is known to be HIV positive since his / her first booster vaccination in precursor Study 700401 (a special HIV test is not required for the purpose of the study); Subject received a blood product or immunoglobulins within 90 days before any blood draw or in the period between the blood draw and the booster vaccination (as applicable); Subject has a known or suspected problem with drug or alcohol abuse (> 4 liters of wine/week or equivalent level of other alcoholic beverages); Subject / parent(s) / legal guardian(s) is / 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 the site conducting the study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>Assessment of seropersistence of TBE antibodies at yearly intervals from approximately 3 years (38 months) to 10 years (118 months) after the first booster vaccination (in Study 700401), as well as antibody response to a second booster vaccination with either FSME-IMMUN 0.25 mL Junior or FSME-IMMUN 0.5 mL, depending on the subject´s age. Timing of the second booster vaccination will depend on the level of serum TBE antibodies detected at the defined assessment time points. Subjects who are not protected against TBE for an entire further season (NT titer <= 20 and/or ELISA value <=126 VIE U/mL) will be invited to receive the second booster vaccination at either the 40, 48, 60, 72, 84, 96, 108, or 120-month time point. | Biological: FSME-IMMUN 0.25 mL Junior (1.2 µg TBE antigen/0.25 mL) or FSME-IMMUN 0.5 mL (2.4µg TBE antigen/0.5 mL)<br>* Dosage form: solution/suspension; injectable. Dosage frequency: once. Mode of administration: intramuscular.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seropositivity Rate Measured by Neutralization Test (NT) at 21-35 Days After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level greater than equal to (>=) 10 at 21-35 days after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent confidence interval (CI) was based upon the observed percentage of participants. | 21-35 days after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 38 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 38 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent confidence interval (CI) was based upon the observed percentage of participants. | 38 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 46 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 46 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 46 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 58 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 58 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 58 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 70 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 70 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 70 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 82 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 82 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 82 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 94 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 94 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 94 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 106 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 106 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 106 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 118 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 118 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 118 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Neutralization Test (NT) at 21-35 Days After the Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 | Seropositivity rate was reported as percentage of participants with NT level >=10 at 21-35 days after the second TBE booster vaccination. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 21-35 days after second TBE booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seropositivity Rate Measured by Enzyme-Linked Immunosorbent Assay (ELISA) at Each Available Time Point After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Seropositivity rate was reported as percentage of participants with ELISA level greater than (>) 126 vienna units per milliliter (VIE U/mL) at each blood sampling time point after first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination | 
| Seropositivity Rate Measured by Enzyme-Linked Immunosorbent Assay (ELISA) at 21-35 Days After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 | Seropositivity rate was reported as percentage of participants with ELISA level >126 VIE U/mL at 21-35 days after second TBE booster vaccination. Exact 2-sided 95 percent CI was based upon the observed percentage of participants. | 21-35 days after second TBE booster vaccination | 
| Geometric Mean Concentration Measured by Enzyme-linked Immunosorbent Assay (ELISA) at Each Available Time-Point After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Antibody against TBE booster vaccination was measured as geometric mean concentration (GMC) by ELISA level at different time points after first booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the concentrations. | 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination | 
| Geometric Mean Concentration Measured by Enzyme-linked Immunosorbent Assay (ELISA) at 21-35 Days After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 | Antibody against TBE booster vaccination was measured as GMC by ELISA level after the second booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the concentrations. | 21-35 days after second TBE booster vaccination | 
| Geometric Mean Titer Measured by Neutralization Test (NT) Each Available Time-Point Blood Draw After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 | Antibody against TBE booster vaccination was measured as geometric mean titer (GMT) by NT level at different time points after first booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers. | 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination | 
| Geometric Mean Titer Measured by Neutralization Test (NT) After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 | Antibody against TBE booster vaccination was measured as GMT by NT level after second booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers. | 21-35 days after second TBE booster vaccination | 
| Geometric Mean Fold Rise (GMFR) in Antibody Concentrations After Second Tick-borne Encephalitis (TBE) Booster Vaccination as Compared to Before the Booster Vaccination as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) | GMFR in antibody concentration from pre-booster (before second booster vaccination) to post-booster (21-35 days after TBE vaccination) was measured by ELISA. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers, concentrations or the fold rises. | Before second booster vaccination (pre-vaccination), 21-35 days after second booster vaccination | 
| Geometric Mean Fold Rise (GMFR) in Antibody Titer After Second Tick-borne Encephalitis (TBE) Booster Vaccination as Compared to Before the Booster Vaccination as Measured by Neutralization Test (NT) | GMFR in antibody titers from pre-booster (before second booster vaccination) to post-booster (21-35 days after TBE vaccination) was measured by ELISA. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers, concentrations or the fold rises. | Before second booster vaccination (pre-vaccination), 21-35 days after second booster vaccination | 
| Number of Participants With Injection Site Reactions and Systemic Reactions After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 | Injection site reactions included swelling, induration, redness, injection site pain, tenderness, ecchymosis and hematoma. Systemic reaction included headache, nausea, vomiting, muscle pain, joint pain, swelling of the lymph nodes, malaise and fatigue. Participants with any injection site reaction and systemic reaction after second TBE booster vaccination in Study 700802 were reported in this outcome measure. | From second booster vaccination up to 21-35 days after the vaccination |