Immunogenicity and Safety of BoostrixTM Using a New Syringe in 10 to 15-year Old Adolescents

Study Overview
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Brief Summary
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The purpose of the study is to compare the immunogenicity and safety of a booster dose of BoostrixTM administered in a new syringe presentation to that of BoostrixTM administered in the previous syringe presentation in healthy adolescents aged 10-15 years.

Detailed Description
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The protocol has been updated following Protocol amendment 1 date 03 August 2011 leading to the update of the exclusion criteria to allow subjects in Mexico to receive the flu vaccine in accordance with the local standard of care. The protocol has been updated following Protocol amendment 2 dated 14 December 2011 due to the recruitment constraints as a result of the DT/dTpa vaccination campaign in the countries. The inclusion and exclusion criteria were amended to allow the participation of those who have already received the 6th dose of the diphtheria, tetanus and/or pertussis containing vaccine.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Boostrix™ Vaccine Using a New Syringe Presentation in Healthy Adolescents Aged 10-15 Years

Conditions
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Diphtheria, Tetanus, Acellular Pertussis

Intervention / Treatment
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* Biological: Boostrix TM (new syringe presentation)
* Biological: Boostrix TM (previous syringe presentation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's parent(s)/Legally Acceptable Representative(s) and subjects who the investigator believes can and are willing to comply with the requirements of the protocol. A male or female between 10 and 15 years of age at the time of booster vaccination. Prior to protocol amendment 2, subjects who have previously received 5 doses of diphtheria-tetanus-pertussis vaccine (whole cell/acellular [w/a]) as part of primary and booster vaccination, in line with local recommendations. After protocol amendment 2, subjects who have previously received 6 doses of either DT(P) (w/a)/ dTpa vaccine as part of primary and booster vaccination, in line with local recommendations. Healthy subjects as determined by the investigator based on medical history and clinical examination before entering into the study. Written informed consent to be obtained before study entry from the parent(s)/ Legally Acceptable Representative(s) of the subject. Written informed assent to be obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative(s), if required by local regulations. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if the subject: has a negative pregnancy test on the day of vaccination, if sexually active, has practiced adequate contraception for 30 days prior to vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after booster vaccination. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine 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. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the booster dose of vaccine - with the exception of influenza vaccine which is allowed up to 7 days before the study vaccine dose, or planned in the period ≥ 7 days after the study vaccine dose. 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. A history of previous or intercurrent diphtheria, tetanus or pertussis disease. A history of vaccination against these diseases since the 5th or the 6th dose of DT(P)/dT(pa). For subjects who have received the 6th dose of the diphtheria, tetanus and/or pertussis containing vaccine, the interval between the last DT(P)/dT(pa) vaccination and the administration of the study vaccine should be at least 18 months. Occurrence of any of the following adverse event after a previous administration of a Boostrix vaccine : known hypersensitivity to any component of the vaccine, or have shown signs of hypersensitivity after previous administration of diphtheria, tetanus or pertussis vaccines, encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis-containing vaccine, transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. Acute disease and/or fever at the time of enrolment. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions, if applicable.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 15 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOOSTRIX NEW GROUP<br>Subjects, aged 10 to 15 years, received one dose of Boostrix™ vaccine administered using a new syringe presentation (prefilled syringes from a different manufacturer) in the deltoid of the non-dominant arm, at Day 0. | Biological: Boostrix TM (new syringe presentation)<br>* Single dose, intramuscular administration in a new syringe presentation<br>|
| Active Comparator: BOOSTRIX PREV GROUP<br>Subjects, aged 10 to 15 years, received one dose of Boostrix™ vaccine administered using a previous syringe presentation (single dose vial or a prefilled disposable syringe without a needle) in the deltoid of the non-dominant arm, at Day 0. | Biological: Boostrix TM (previous syringe presentation)<br>* Single dose, intramuscular administration in previous syringe presentation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). | At Month 1 | 
| Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter(EL.U/mL) | At Month 1 | 
| Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). | At Day 0 | 
| Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). | At Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects Against Diphtheria (D) and Tetanus (T) Antigens | A seroprotected subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 0.1. international units per milliliter (IU/mL), as assessed by the Enzyme Linked Immunosorbent Assay (ELISA). | At Day 0 (PRE) and at Month 1 (POST) | 
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigens | A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to ( ≥) 1 international units per milliliter (IU/mL). | At Day 0 (PRE) vaccine and at Month 1 (POST) | 
| Number of Seropositive Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations) | A seroprotected subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 5 Enzyme Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL). | At Day 0 (PRE) vaccine and at Month 1 (POST) | 
| Number of Subjects With Booster Response to Diphtheria (D) and Tetanus (T) Antibodies | Booster response to the diphtheria and tetanus antigens, was defined as: for initially seronegative subjects (pre-vaccination concentration <0.1 IU/mL): antibody concentrations at least 4 times the cut-off (post-vaccination concentration ≥ 0.4 IU/mL); for initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least 4 times the pre-vaccination concentration. | At Month 1 | 
| Number of Subjects With a Booster Response to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) Antigens. | Booster response to the PT, FHA and PRN antigens, was defined as: for initially seronegative subjects: antibody concentrations at least 4 times the cut-off (post-vaccination concentration ≥ 20 EL.U/mL); for initially seropositive subjects with pre-vaccination concentration ≥ 5 EL.U/mL and < 20 EL.U/mL: an increase in antibody concentrations of at least 4 times the pre-vaccination concentration; and for initially seropositive subjects with pre-vaccination concentration ≥ 20 EL.U/mL: an increase in antibody concentrations of at least 2 times the pre-vaccination concentration. | At Month 1 | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | Within 4 days (Days 0-3) post vaccination period | 
| 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 and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | Within 31 days (Days 0-30) post | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were fatigue, temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache and gastrointestinal symptoms. Gastrointestinal symptoms included Nausea, Vomiting, Diarrhea and or Abdominal pain. Any = occurrence of the symptom regardless of intensity grade. | Within 4 days (Days 0-3) post vaccination period | 
| Number of Subjects With 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 or result in disability/incapacity. | During the entire study period (Day 0 - Month 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dTpa, Boostrix