The Aim of This Study is to Investigate the Persistence of Antibody Response in Adults up to 15 Years After One Booster Dose of GlaxoSmithKline (GSK) Biologicals' Encepur Adults Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to continue the evaluation of antibody persistence through 11 to 15 years after first booster with Tick-Borne Encephalitis (TBE) vaccine. This study will further investigate the booster response in subjects who will receive their second booster dose* in this study. * Any booster given in this study will be the second that the subject has received (with regard to the follow-up of the previous study).

Official Title
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Long Term Immunogenicity up to 15 Years After the First Booster Immunization With GSK Biologicals' Encepur Adults (Polygeline-free Tick-Borne Encephalitis Vaccine for Adults) in Adults Who Received 1 of 3 Different Primary Vaccination Schedules

Conditions
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Virus Diseases

Intervention / Treatment
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* Biological: Encepur Adults


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for all subjects: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written informed consent obtained from the subject prior to performance of any study specific procedure. Subjects who have participated in study V48P7E2 (NCT01562444) and who received in the parent V48P7 study one of the following schedules: rapid, conventional, or accelerated conventional and a booster vaccination in study V48P7E1 (NCT00387634) or before study V48P7E1 (NCT00387634) (only rapid schedule). Additional inclusion criteria for subjects who will need a second booster dose: Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Female subjects of childbearing potential can receive the booster vaccine in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after booster administration. Exclusion Criteria: Each subject must not be: Unwilling or unable to give written informed consent to participate in the study. Perceived to be unreliable or unavailable to complete the study. Each subject must not have: Clinical conditions representing a contraindication to blood draws. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. Received an investigational or non-registered medicinal product within 30 days prior to informed consent. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product. Levels of NT<10 in V48P7E2 (NCT01562444) study. Previous vaccination against TBE or other Flavivirus diseases with other TBE and Flavivirus vaccines (e.g. Yellow fever vaccine, Dengue fever vaccine, Japanese encephalitis vaccine) before, during and after completion of the V48P7E2 (NCT01562444) and before starting TBEV POLYGELINE FREE-025 EXT 21 study. Primary immunization with TBE vaccine in the parent study V48P7 according to the modified conventional (MC) schedule. History of confirmed TBE infection. Known exposure to other Flaviviruses. Each subject who will receive the second booster vaccination in this study additionally to the exclusion criteria above must not have: Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. Clinical conditions representing a contraindication to intramuscular vaccination. Progressive, unstable or uncontrolled clinical conditions. Abnormal function of the immune system resulting from: Clinical conditions. Systemic administration of corticosteroids for more than 14 consecutive days within 90 days prior to informed consent. This will mean prednisone ≥20 mg/day (for adult subjects) or equivalent. Inhaled and topical steroids are allowed. Administration of antineoplastic and immuno-modulating agents or radiotherapy within 90 days prior to vaccination. Received immunoglobulins or any blood products within 180 days prior to vaccination. Administration of long-acting immune-modifying drugs at any time during the study period. Acute disease and/or fever at the day of booster vaccination. Expected general decrease in immune response. Organic brain disturbances, including seizure disorders. Progressive neurological disorders. Suffered febrile or afebrile convulsions. Serious chronic illness. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or chemically related substances. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination in this study or who are planning to receive any vaccine within 28 days from the study vaccines. Pregnant.

Ages Eligible for Study
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Minimum Age: 25 Years

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
Intervention Model: Parallel Assignment
Interventional Model Description: All subjects will come to the yearly scheduled blood draw visit for investigation of 11 to 15 year persistence of Neutralization Test (NT) titres. Subjects who have an NT titre below 10 at one of the scheduled visits will receive a second booster dose 6 months after this visit at an unscheduled visit. Subsequent data of these subjects will be analysed separately in a subgroup.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional Group<br>Subjects will receive a second booster vaccination six months after the blood draw only in case they result to be with an NT titre below 10 and who belonged to the following vaccination schedule in the primary studies: Primary vaccination of 66 subjects in study V48P7 on Days 0, 28 (+10) and 300 (+21), booster vaccination of 55 subjects in study V48P7E1 (NCT00387634), no vaccination in study TBEV POLYGELINE FREE (V48)-023 EXT 021 (V48P7E2) (NCT01562444). | Biological: Encepur Adults<br>* One dose of the vaccine can be administered at any one unscheduled visit depending on the detection of NT below 10. It will be administered intramuscularly into the non-dominant deltoid.<br>|
| Experimental: Accelerated/Rapid Group<br>Subjects will receive a second booster vaccination six months after the blood draw only in case they result to be with an NT titre below 10 and who belonged to the following vaccination schedule in the primary studies: Primary vaccination of 66 subjects in study V48P7 on Days 0, 7 (+3) and 21 (+7), booster vaccination of 9 subjects in study V48P7E1 (NCT00387634) 40 subjects received their booster vaccination before enrolment in study V48P7E1 (NCT00387634), no vaccination in study TBEV POLYGELINE FREE (V48)-023 EXT 021 (V48P7E2) (NCT01562444). | Biological: Encepur Adults<br>* One dose of the vaccine can be administered at any one unscheduled visit depending on the detection of NT below 10. It will be administered intramuscularly into the non-dominant deltoid.<br>|
| Experimental: Accelerated Conventional Group<br>Subjects will receive a second booster vaccination six months after the blood draw only in case they result to be with an NT titre below 10 and who belonged to the following vaccination schedule in the primary studies: Primary vaccination of 133 subjects in study V48P7 on Days 0, 14 (+3) and 300 (+21), booster vaccination of 109 subjects in study V48P7E1 (NCT00387634), no vaccination in study TBEV POLYGELINE FREE (V48)-023 EXT 021 (V48P7E2) (NCT01562444). | Biological: Encepur Adults<br>* One dose of the vaccine can be administered at any one unscheduled visit depending on the detection of NT below 10. It will be administered intramuscularly into the non-dominant deltoid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 11 | 
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 12 | 
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 13 | 
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 14 | 
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 15 | 
| Geometric Mean Antibody Titres as measured by GSK Biologicals' NT calculated for each of the different schedule groups. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 11 | 
| Geometric Mean Antibody Titres as measured by GSK Biologicals' NT calculated for each of the different schedule groups. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 12 | 
| Geometric Mean Antibody Titres as measured by GSK Biologicals' NT calculated for each of the different schedule groups. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 13 | 
| Geometric Mean Antibody Titres as measured by GSK Biologicals' NT calculated for each of the different schedule groups. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 14 | 
| Geometric Mean Antibody Titres as measured by GSK Biologicals' NT calculated for each of the different schedule groups. | This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years. | At Year 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Biologicals' NT, overall and by study group. | This endpoint will be summarized according to the primary immunization schedule received in the parent study (V48P7). | At 21 days after the booster vaccination | 
| Geometric Mean Antibody Titres and Geometric Mean Ratios (GMRs) blood draw after/before booster as measured by GSK Biologicals' NT, overall and by study group. | This endpoint will be summarized according to the primary immunization schedule received in the parent study (V48P7). | At 21 days after the booster vaccination | 
| Thorough description of NT waning in order to complement the analysis of persistence. | This endpoint will be summarized according to the primary immunization schedule received in the parent study (V48P7). To complement the analysis of persistence, a thorough description of NT waning from year 1 after the first booster dose up to 15 years will be presented for the set of subjects completing the entire 15-year follow-up with no protocol deviations, including those receiving a second booster dose; for whom, a constant value of NT = 1 from the post booster visit will be used in the analysis. | At 21 days after the booster vaccination | 
| Incidence of serious adverse events (SAEs). | The safety endpoint for subjects who will need a second booster vaccination will be based on SAEs collection after the second booster dose. SAEs are defined as any untoward medical occurrence that results in death, is life- threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. | At 1 month after vaccination. Based on the timing of the booster dose, at years 11.5 (Visit 23.1), 12.5 (Visit 24.1), 13.5 (Visit 25.1), or 14.5 (Visit 26.1) or from year 15.5 (Visit 27.1) until 21 days after year 15.5 (Visit 27.2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Booster, Encepur, Adults, Long term immunogenicity, Tick-borne Encephalitis vaccine