Evaluation of Boostrix™10 Years After Previous Booster Vaccination

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the immunogenicity, safety and reactogenicity of a dTpa (Boostrix™ vaccine) booster dose given 10 years after the previous vaccination with dTpa in GSK 263855/029 study. Only subjects who were part of the primary study will be invited to participate in this study.This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate study (see reference).

Detailed Description
-----------------
All subjects will receive a booster dose of the vaccine that they received in their primary study. Subjects who received the investigational vaccine formulation, will receive Boostrix™ in the present study.

Official Title
-----------------
Evaluation of GSK Biologicals' Boostrix™ in Healthy Adults, 10 Years After Previous Booster Vaccination

Conditions
-----------------
Acellular Pertussis, Tetanus, Diphtheria

Intervention / Treatment
-----------------
* Biological: Boostrix™
* Biological: Boostrix™-US formulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Male or female subjects who have received Boostrix™, Boostrix™-US formulation or the investigational vaccine formulation in the study 263855/029. Written informed consent obtained from the subject. Additional criteria to be checked before the booster vaccination. Healthy subjects as established by medical history and clinical examination. Female subjects of non-childbearing potential may receive the booster vaccine. Female subjects of childbearing potential may receive the booster vaccine, if the subject: practices/has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and agrees to continue adequate contraception during the entire booster epoch. Exclusion Criteria: Exclusion criteria to be checked at study entry: Previous booster vaccination against diphtheria, tetanus, or pertussis since the dose received in the study 263855/029. History of diphtheria, tetanus, or laboratory confirmed pertussis disease. Any confirmed or suspected immunosuppressive or immunodeficiency condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus. Occurrence of any of the following adverse event after a previous administration of a DTP vaccine : hypersensitivity reaction to any component of the vaccine, encephalopathy of unknown aetiology occurring within seven days following previous vaccination with pertussis-containing vaccine, fever >= 40 °C (axillary temperature) within 48 hours of vaccination not due to another identifiable cause, collapse or shock-like state within 48 hours of vaccination, convulsions with or without fever, occurring within three days of vaccination. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Additional exclusion criteria to be checked for subjects before the booster vaccination administration: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the booster dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to booster vaccination, or planned administration during the active study period. 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 product. Administration of immunoglobulins and/or any blood products within the three months preceding the booster dose or planned administration during the study period. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 28 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boostrix-REF Group<br>Subjects in this group were healthy adult subjects aged 18 to 28 years at the time of enrolment and with previous completed primary and booster vaccination with a diphtheria-tetanus-whole cell pertussis vaccine completed by one additional booster dose of Boostrix™ vaccine, reference formulation, at Day 0 in GSK 263855/029 study. These subjects received, as part of this NCT01147900 study, one further booster dose of Boostrix™ vaccine, reference formulation, at Year 10, 10 years after booster vaccination in the GSK 263855/029 study. The Boostrix™ vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. | Biological: Boostrix™<br>* Intramuscular, single dose<br>|
| Experimental: Boostrix-US Group<br>Subjects in this group were healthy adult subjects aged 18 to 28 years at the time of enrolment and with previous completed primary and booster vaccination with a diphtheria-tetanus-whole cell pertussis vaccine completed by one additional booster dose of Boostrix™ vaccine, United States(US)-marketed formulation, at Day 0 in GSK 263855/029 study. These subjects received, as part of this NCT01147900 study, one further booster dose of Boostrix™ vaccine, US-marketed formulation, at Year 10, 10 years after booster vaccination in the GSK 263855/029 study. The Boostrix™ vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. | Biological: Boostrix™-US formulation<br>* Intramuscular, single dose<br>|
| Experimental: Boostrix-INV Group<br>Subjects in this group were healthy adult subjects aged 18 to 28 years at the time of enrolment and with previous completed primary and booster vaccination with a diphtheria-tetanus-whole cell pertussis vaccine completed by one additional booster dose of Boostrix™ vaccine, investigational formulation, at Day 0 in GSK 263855/029 study. These subjects received, as part of this NCT01147900 study, one further booster dose of Boostrix™ vaccine, reference formulation, at Year 10, 10 years after booster vaccination in the GSK 263855/029 study. The Boostrix™ vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm. | Biological: Boostrix™<br>* Intramuscular, single dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria and Tetanus | A subject seroprotected against diphtheria/tetanus was defined as a vaccinated subject who had an anti-diphtheria (anti-D)/anti-tetanus (anti-T) antibody concentration greater than or above (≥) 0.1 international units per milliliter (IU/mL). | At Year 8.5 | 
| Concentrations for Anti-D and Anti-T Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL for all antibodies assessed. | At Year 8.5 | 
| Number of Seroprotected Subjects Against Diphtheria and Tetanus. | A subject seroprotected against diphtheria/tetanus was defined as a vaccinated subject who had an anti-D/anti-T antibody concentration greater than or above (≥) 0.1 international units per milliliter (IU/mL). | At Year 10 | 
| Concentrations for Anti-D and Anti-T Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL. | At Year 10 | 
| Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Haemagglutinin (Anti-FHA) Antibodies. | A seropositive subject for anti-PT/anti-PRN/anti-FHA antibodies was defined as a vaccinated subject who had anti-PT/anti-PRN/anti-FHA antibody concentrations greater than or equal to (≥) 5 Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Year 8.5 | 
| Concentrations for Anti-PT, Anti-PRN and Anti-FHA Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 5 EL.U/mL for all antibodies assessed. | At Year 8.5 | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies. | A seropositive subject for anti-PT/anti-FHA/anti-PRN antibodies was defined as a vaccinated subject who had anti-PT/anti-FHA/anti-PRN antibody concentrations greater than or equal to (≥) 5 Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Year 10 | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 5 EL.U/mL. | At Year 10 | 
| Number of Seroprotected Subjects Against Diphtheria and Tetanus | A subject seroprotected against diphtheria/tetanus was defined as a vaccinated subject who had an anti-D/anti-T antibody concentration greater than or above (≥) 0.1 international units per milliliter (IU/mL). | At Year 10 pre booster vaccination (PRE) and at 1 month post Year 10 booster vaccination (POST) | 
| Concentrations for Anti-D and Anti-T Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection cut-off of the assay was 0.1 IU/mL for all antibodies assessed. | At Year 10 pre booster vaccination (PRE) and at 1 month post Year 10 booster vaccination (POST) | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies. | A seropositive subject for anti-PT/anti-PRN/anti-FHA antibodies was defined as a vaccinated subject who had anti-PT/anti-PRN/anti-FHA antibody concentrations greater than or equal to (≥) 5 ELISA units per milliliter (EL.U/mL). | At Year 10 pre booster vaccination (PRE) and at 1 month post Year 10 booster vaccination (POST) | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN Antibodies. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity cut-off of the assay was 5 EL.U/mL. | At Year 10 pre booster vaccination (PRE) and at 1 month post Year 10 booster vaccination (POST) | 
| Number of Booster Responders to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens. | A booster responder to PT/PRN antigens was defined as either a vaccinated subject seronegative at analysis baseline (Year 10) with anti-PT/anti-PRN antibody concentration greater than or equal to (≥) 5 EL.U/mL at one month post Year 10 booster vaccination, or as a vaccinated subject seropositive at analysis baseline (Year 10) and with anti-PT/anti-PRN antibody concentration with at least a 2-fold increase at one month post Year 10 booster vaccination. A seronegative/seropositive subject was defined as a vaccinated subject with anti-PT/anti-PRN antibody concentration ≥/< 5 EL.U/mL. | At 1 month post Year 10 booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = incidence of a particular symptom regardless of intensity grade. | During the 4-day (Days 0-3) follow-up period after booster vaccination | 
| Number of Subjects With Any Solicited General Symptoms. | Assessed solicited general symptoms were fatigue, gastrointestinal, headache and fever [defined as axillary temperature ≥ 37.5 degrees Celsius (°C)]. Any = incidence of a particular symptom regardless of intensity grade and relationship to vaccination. | During the 4-day (Days 0-3) follow-up period after booster vaccination | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs). | An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any unsolicited AE = any unsolicited AE regardless of intensity or relationship to vaccination. | During the 31-day (Days 0-30) follow-up period after booster vaccination | 
| Number of Subjects With Any Serious Adverse Events (SAEs). | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.. | At Year 8.5 | 
| Number of Subjects With Any Serious Adverse Events (SAEs). | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From Year 8.5 up to study end (one month post Year 10 booster vaccination) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune persistence, Boostrix, dTpa booster study