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

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

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).

Study Overview

• Status: Completed
• Conditions: Virus Diseases
• Intervention / Treatment: Biological: Encepur Adults

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 4

Contacts and Locations

Study Locations

• Czechia
  • Hradec Kralove, Czechia, 50002
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional Group; Participants who received primary vaccination in study V48P7 on Days 0, 28 (+10) and 300 (+21) (55 participants) and who received a booster vaccination in study V48P7E1 (NCT00387634) (55 participants). For these participants a second booster vaccination within six months after the annual blood draw was to be administered within the present study only in case their Neutralization Test (NT) titer resulted below 10.	Biological: Encepur Adults; 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.
Experimental: Accelerated/Rapid Group; Participants who received primary vaccination in study V48P7 on Days 0, 7 (+3) and 21 (+7) (66 participants) and who received a booster vaccination either in study V48P7E1 (NCT00387634) (9 participants) or before enrolment in study V48P7E1 (NCT00387634) (40 participants). For these participants a second booster vaccination within six months after the annual blood draw was to be administered within the present study only in case their NT titer resulted below 10.	Biological: Encepur Adults; 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.
Experimental: Accelerated Conventional Group; Participants who received primary vaccination in study V48P7 on Days 0, 14 (+3) and 300 (+21) (133 participants) and who received a booster vaccination in study V48P7E1 (NCT00387634) (109 participants). For these participants a second booster vaccination within six months after the annual blood draw was to be administered within the present study only in case their NT titer resulted below 10.	Biological: Encepur Adults; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 11	Antibody titers were measured by GSK Biologicals' Neutralization test. Analysis of the percentages of participants with antibody titers >= 2 was not performed as planned in the protocol, as only 3 participants had antibody titers between 2 and 10 during the whole study period.	At Year 11
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 12	Antibody titers were measured by GSK Biologicals' Neutralization test. Analysis of the percentages of participants with antibody titers >= 2 was not performed as planned in the protocol, as only 3 participants had antibody titers between 2 and 10 during the whole study period.	At Year 12
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 13	Antibody titers were measured by GSK Biologicals' Neutralization test. Analysis of the percentages of participants with antibody titers >= 2 was not performed as planned in the protocol, as only 3 participants had antibody titers between 2 and 10 during the whole study period.	At Year 13
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 14	Antibody titers were measured by GSK Biologicals' Neutralization test. Analysis of the percentages of participants with antibody titers >= 2 was not performed as planned in the protocol, as only 3 participants had antibody titers between 2 and 10 during the whole study period.	At Year 14
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 15	Antibody titers were measured by GSK Biologicals' Neutralization test. Analysis of the percentages of participants with antibody titers >= 2 was not performed as planned in the protocol, as only 3 participants had antibody titers between 2 and 10 during the whole study period.	At Year 15
Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 11	Immunogenicity was measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at Year 11. GMTs were assessed for following age subgroups: 25 to 49 years, equal to or above (>=) 50 years and >= 60 years.	At Year 11
Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 12	Immunogenicity was measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at Year 12. GMTs were assessed for following age subgroups: 25 to 49 years, >= 50 years and >= 60 years.	At Year 12
Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 13	Immunogenicity was measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at Year 13. GMTs were assessed for following age subgroups: 25 to 49 years, >= 50 years and >= 60 years.	At Year 13
Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 14	Immunogenicity was measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at Year 14. GMTs were assessed for following age subgroups: 25 to 49 years, >= 50 years and >= 60 years.	At Year 14
Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 15	Immunogenicity was measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at Year 15. GMTs were assessed for following age subgroups: 25 to 49 years, >= 50 years and >= 60 years.	At Year 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 2 and Equal to or Above 10 as Measured by GSK Biologicals' NT, Overall and by Study Group	Immunogenicity was planned to be measured in terms of percentage of participants with TBE Neutralizing Antibody Titers >= 2 and >= 10 at 21 days after the booster vaccination.	At 21 days after the booster vaccination
Geometric Mean Antibody Titers (GMTs) as Measured by GSK Biologicals' NT, Overall and by Study Group	Immunogenicity was planned to be measured in terms of GMTs of serum TBE Neutralizing Antibody Titers at 21 days after the booster vaccination.	At 21 days after the booster vaccination
Geometric Mean Ratios (GMRs) Blood Draw After/Before Booster as Measured by GSK Biologicals' NT, Overall and by Study Group	Immunogenicity was planned to be measured in terms of GMRs of serum TBE Neutralizing Antibody Titers at 21 days after the booster vaccination.	At 21 days after the booster vaccination
Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to and Above 10 as Measured by GSK Biologicals' NT, Overall and by Study Group	Immunogenicity was measured in terms of percentage of participants with TBE Neutralizing Antibody Titers >= 10 from Year 1 to Year 15.	From Year 1 up to Year 15
Number of Participants With Serious Adverse Events (SAEs)	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.	From Day 0 to Day 21 after booster vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

General Publications

• Beran J, Lattanzi M, Costantini M, Pammolli A, Galgani I. Sustained antibody persistence for at least 15 years after a booster vaccination against tick-borne encephalitis following different primary vaccination schedules: Third 5-year follow-up. Vaccine. 2023 May 26;41(23):3518-3524. doi: 10.1016/j.vaccine.2023.04.061. Epub 2023 May 3.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): October 25, 2021

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Booster; Adults; Encepur; Long term immunogenicity; Tick-borne Encephalitis vaccine
• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: 205847; 2017-001356-59 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No