Clinical trial NCT03294135: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Virus Diseases
Keywords: Encepur
Adults
Long term immunogenicity
Tick-borne Encephalitis vaccine
Booster
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-09-26
Enrollment: 194
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 11
timeFrame: At Year 11
measure: Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 12
timeFrame: At Year 12
measure: Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 13
timeFrame: At Year 13
measure: Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 14
timeFrame: At Year 14
measure: Percentage of Participants With Detectable TBE Neutralizing Antibody Titers Equal to or Above 10 at Year 15
timeFrame: At Year 15
measure: Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 11
timeFrame: At Year 11
measure: Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 12
timeFrame: At Year 12
measure: Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 13
timeFrame: At Year 13
measure: Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 14
timeFrame: At Year 14
measure: Geometric Mean Antibody Titers (GMTs) by Age Categories at Year 15
timeFrame: At Year 15
Secondary outcomes:
measure: 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
timeFrame: At 21 days after the booster vaccination
measure: Geometric Mean Antibody Titers (GMTs) as Measured by GSK Biologicals' NT, Overall and by Study Group
timeFrame: At 21 days after the booster vaccination
measure: Geometric Mean Ratios (GMRs) Blood Draw After/Before Booster as Measured by GSK Biologicals' NT, Overall and by Study Group
timeFrame: At 21 days after the booster vaccination
measure: 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
timeFrame: From Year 1 up to Year 15
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Day 0 to Day 21 after booster vaccination
Other outcomes:
Locations:
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.