Immunogenicity, Safety of GSKs Tdap Vaccine Boostrix When Coadministered With GSKs Influenza Vaccine Fluarix in Adults

Study Overview
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Brief Summary
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The current study will provide information for the use of Boostrix concomitantly with influenza vaccine in adults aged 19-64 years. This study will also provide safety and immunogenicity data in a cohort of adults aged greater than or equal to 65 years.

Official Title
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A Study to Evaluate Immunogenicity and Safety of Boostrix When Co-administered With Fluarix in Subjects 19 Years of Age and Older

Conditions
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Acellular Pertussis, Diphtheria, Tetanus

Intervention / Treatment
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* Biological: Fluarix®
* Biological: Boostrix®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female adults aged between 19 to 64 years, inclusive for the primary cohort), or aged 65 years or older (for the exploratory cohort), at the time of vaccination. Exclusion Criteria: Administration of an influenza vaccine within six months prior to study entry Administration of a diphtheria-tetanus (Td) booster within the previous 5 years. Administration of a Tdap vaccine at any time prior to study entry. Administration of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding vaccination, or planned use during the entire study period. History of diphtheria and/or tetanus and/or pertussis disease. History of serious allergic reaction (e.g. anaphylaxis) following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine or influenza vaccine or any component of the study vaccines.

Ages Eligible for Study
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Minimum Age: 19 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOOSTRIX+FLUARIX GROUP<br>Healthy male or female adults, aged between 19 to 64 years of age inclusive and 65 years or older, who received Boostrix® vaccine co-administered with Fluarix® vaccine at Day 0, injected intramuscularly in the left and right upper deltoid regions, respectively. | Biological: Fluarix®<br>* GSK Biologicals' inactivated influenza split virus vaccine.<br>Biological: Boostrix®<br>* GSK Biologicals' tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.<br>|
| Experimental: FLUARIX BOOSTRIX GROUP<br>Healthy male or female adults, aged between 19 to 64 years of age inclusive and 65 years or older, who received Fluarix® vaccine at Day 0 and Boostrix® vaccine at Month 1, both injected intramuscularly in the upper left deltoid region. | Biological: Fluarix®<br>* GSK Biologicals' inactivated influenza split virus vaccine.<br>Biological: Boostrix®<br>* GSK Biologicals' tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Toxoid Antigens | A seroprotected subject was defined as a vaccinated subject with anti-D and anti-T antibody concentrations equal to or above (≥) 0.1 International Units per milliliter (IU/mL), respectively. | At Month 1 post-Boostrix® vaccination | 
| Number of Subjects With Anti-T Antibody Concentrations ≥ the Assay Cut-off Value | The assay cut-off value was ≥ 1.0 IU/mL, as assessed by enzyme-linked immunosorbent assay (ELISA). | At Month 1 post-Boostrix® vaccination | 
| Antibody Concentrations Against Pertussis Toxoid (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antigens | Anti-PT, anti-FHA and anti-PRN antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). | At Month 1 post-Boostrix® vaccination | 
| Number of Subjects With Serum Haemagglutinin Inhibition (HI) Titers Against 3 Strains of Influenza | The antibody titer cut-off value for the 3 influenza strains assessed (H1N1, H3N2 and B) was ≥ 1:40. | At Month 1 post-Fluarix® vaccination | 
| Number of Seroconverted Subjects Against Influenza Antigens H1N1, H3N2, and B | Seroconversion for HI antibodies is defined as: For initially seronegative subjects: post-vaccination antibody titer ≥ 1:40 at Month 1 post-Boostrix® vaccination; For initially seropositive subjects: antibody titer at Month 1≥ 4 fold the pre-vaccination antibody titer. | At Month 1 post-Fluarix® vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects With Anti-D Antibody Concentrations Above the Cut-off Value | A seropositive subject was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value of 1.0 IU/mL. | At Month 1 post-Boostrix® vaccination | 
| Antibody Concentrations for Diphteria Toxoid (D) and Tetanus Toxoid (T) | Anti-D and anti-T antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in International Units per milliliter (IU/mL). | At Day 0 and Month 1 post-Boostrix® vaccination | 
| Antibody Concentrations for Pertussis Toxoid (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) | Anti-PT, anti-FHA and anti-PRN antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). | At Day 0 and Month 1 post-Boostrix® vaccination | 
| Number of Subjects With Booster Response Against Diphteria Toxoid (D) and Tetanus Toxoid (T) Antigens | Booster responses for anti-D and anti-T antibodies are defined as: For initially seronegative subjects [pre-vaccination concentration below (<) cut-off 0.1 IU/mL]: antibody concentrations at least four times the assay cut-off (post-vaccination concentration ≥ 0.4 IU/mL), one month after vaccination with Boostrix®; For initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration, one month after vaccination with Boostrix®. | At Month 1 post-Boostrix® vaccination | 
| Number of Subjects With Booster Response Against Pertussis Toxoid (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antigens | Booster responses for anti-PT, anti-FHA and anti-PRN are defined as: For initially seronegative subjects (pre-vaccination concentration < cut-off of 5 EL.U/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration ≥ 20 EL.U/mL), one month after vaccination with Boostrix®; 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 four times the pre-vaccination concentration one month after vaccination with Boostrix®; For initially seropositive subjects with pre-vaccination concentration ≥ 20 EL.U/mL: an increase in antibody concentrations of at least two times the pre-vaccination concentration one month after vaccination with Boostrix®. | At Month 1 post-Boostrix® vaccination | 
| Anti-H1N1, Anti-H3N2 and Anti-B Antibody Titers | Anti-H1N1, anti-H3N2 and anti-B antibody titers are presented as geometric mean titers (GMTs). | At Month 1 post-Fluarix® vaccination | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Subjects from Boostrix+Fluarix Groups (19-64 YOA and ≥ 65 YOA) received only one vaccination dose (Boostrix® vaccine co-administered with Fluarix® vaccine), at Day 0. | During the 15-day (Day 0-14) period following each dose and across doses, up to 2 months | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal (nausea, vomiting, diarrhoea and/or abdominal pain), headache, joint pain, muscle aches and shivering. Any = occurrence of the symptom regardless of intensity grade or relationship to the study vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Subjects from Boostrix+Fluarix Groups (19-64 YOA and ≥ 65 YOA) received only one vaccination dose (Boostrix® vaccine co-administered with Fluarix® vaccine), at Day 0. | During the 15-day (Day 0-14) period following each dose and across doses, up to 2 months | 
| Number of Subjects With Any 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. | During the 31-day period (Day 0-30) following each vaccination, up to 2 months | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | Throughout the whole study period (from Day 0 to Month 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity,, Influenza, Co-administration,, Tdap,