Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Boostrix™ Vaccine in Previously Boosted Young Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of this follow-up study is to evaluate the persistence of antibodies against all the vaccine antigens 10 years after booster vaccination with either Tdap or Td, and also to assess immunogenicity and safety of another dose of Boostrix, administered in this study. This protocol posting deals with objectives and outcome measures of the extension phase. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00109330).

Detailed Description
-----------------
Subjects were previously vaccinated with either Boostrix or a control Td vaccine in study NCT00109330. Only subjects who were part of the primary study will be invited to participate in this study. All subjects will receive a single dose of Boostrix at Visit 1 (Day 0) and subjects will be observed till Visit 2 (Day 30) for safety in terms of solicited adverse events (during 4 days post vaccination), unsolicited adverse events (during 31 days post vaccination) and serious adverse event (during the trial period). A blood sample will be collected from all subjects before vaccination (Visit 1) and one month after vaccination (Visit 2) for antibodies estimation. This summary has been updated following Protocol amendment 2 dated 03 October 2013. The protocol is being amended to facilitate enrolment by: - Extending the window period for re-vaccination from ± 6 months to ± 300 days from the Year 10 time point. - Extending the recruitment period from 6 months to 14 months. The format of non-inferiority criterion of the first co-primary objective has been updated to keep it aligned with the format of non-inferiority criterion of the second co-primary objective.

Official Title
-----------------
Evaluation of Immunogenicity and Safety of GSK Biologicals' Tdap Booster Vaccine (Boostrix™) in Young Adults, Administered 10 Years After Previous Tdap Boosting

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

Intervention / Treatment
-----------------
* Biological: Boostrix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit). Subjects who have received a dose of Tdap or Td vaccines 10 years (+/-300 days) back, in study NCT00109330. Written informed consent obtained from the subject. 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 tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled 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 during the entire treatment period and for 1 month after completion of the vaccine dose. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose . For corticosteroids, this will mean prednisone (≥ 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 31 days after the dose of vaccine, with the exception of Influenza vaccine which is allowed throughout the 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 vaccine/product (pharmaceutical product or device). Previous vaccination against diphtheria, tetanus or pertussis since the last dose received in the Study NCT00109330. History of diphtheria, tetanus or pertussis diseases following the receipt of booster dose in the Study NCT00109330. Severe allergic reaction (e.g. anaphylaxis) after previous administration of any tetanus toxoid, diphtheria toxoid, or pertussis-antigen containing vaccines, or any component of Boostrix. Hypersensitivity to latex. Encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) of unknown etiology occurring within 7 days following previous vaccination with pertussis-containing vaccine. History of any neurological disorders or seizures. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 99.5°F for oral, axillary or tympanic route, or ≥ 100.4°F for rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the 3 months preceding the booster dose of study vaccine or planned administration during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions up to 1 month post-vaccination.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 30 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 Group 2<br>Healthy male of female subjects, aged 19 to 30 years of age at the time of booster vaccination, who were randomized to the Lot A, Lot B or Lot C groups in study NCT00109330, received a second dose of Boostrix in this study. | Biological: Boostrix<br>* Single dose intramuscular administration.<br>|
| Active Comparator: Boostrix Group 1<br>Healthy male of female subjects, aged 19 to 30 years of age at the time of booster vaccination, who received Massachusetts Public Health Biologic Laboratories combined tetanus and diphtheria vaccine in study NCT00109330, received the first dose of Boostrix in this study. | Biological: Boostrix<br>* Single dose intramuscular administration.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T). | A seroprotected subject was defined as a subject with anti-D/anti-T antibody concentrations above or equal (≥) to 0.1 IU/mL (international units per milliliter) | At Month 1 | 
| Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Against Filamentous Hemagglutinin (Anti-FHA) and Against Pertactin (Anti-PRN). | Concentrations were expressed in geometric mean concentrations (GMCs). | At Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T). | A seroprotected subject was defined as a subject with anti-D/anti-T antibody concentrations above or equal (≥) to 0.1 IU/mL (international units per milliliter) | At Month 0 | 
| Number of Subjects With Anti-D and Anti-T Concentrations Above the Cut-off. | The cut-off of the assay was ≥ 1.0 IU/mL. | At Month 0 and Month 1 | 
| Anti-D and Anti-T Antibody Concentrations. | Concentrations were expressed as GMCs. | At Month 0 and Month 1 | 
| Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Against Filamentous Hemagglutinin (Anti-FHA) and Against Pertactin (Anti-PRN). | Concentrations were expressed in geometric mean concentrations (GMCs). | At Month 0 | 
| Number of Subjects With a Booster Response to Anti-D and Anti-T. | Booster response to anti-D and anti-T antigens was defined as: for initially seronegative subjects with pre-booster antibody concentration below 0.1 IU/mL, an increase of at least four times 0.1 IU/mL one month after vaccination, for initially seropositive subjects with pre-booster antibody concentration ≥ 0.1 IU/mL, an increase of at least four times the pre-booster antibody concentration one month after vaccination. | At Month 1 | 
| Number of Subjects With a Booster Response to Anti-PT, Anti-FHA and Anti-PRN. | Booster response to pertussis antigens was defined as: for initially seronegative subjects (pre-booster antibody concentration below the assay cut-off) with an increase of at least four times the assay cut-off one month after vaccination; for initially seropositive subjects with anti-body concentration < four times the assay cut-off with an increase of at least four times the pre-booster antibody concentration one month after vaccination; for initially seropositive subjects with anti-body concentration ≥ four times the assay cut-off with an increase of at least two times the pre-booster antibody concentration one month after vaccination. | At Month 1. | 
| Number of Subjects With Solicited Local Symptoms. | The solicited local symptoms assessed were Pain, Redness and Swelling. Any = any solicited local symptom regardless of intensity. | During the 4 days (Day 0 - 3) follow-up period after vaccination. | 
| Number of Subjects With Solicited General Symptoms. | The solicited local symptoms assessed were Fatigue, Gastrointestinal, Headache and Fever. Any = any solicited general symptom regardless of intensity. | During the 4 days (Day 0 - 3) follow-up period after vaccination. | 
| Number of Subjects With Unsolicited Adverse Events (AEs). | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. | During the 31 days (Day 0 - 30) after vaccination. | 
| Number of Subjects With Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that results in death, are life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. | From Day 0 to 31 days post-vaccination. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Booster, Tdap, Immunogenicity, Repeat dose, Safety, BoostrixTM, Persistence