Safety and Immunogenicity of GSK's Tdap Vaccine (Boostrix) in Adults Aged 19 to 64 Years

Study Overview
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Brief Summary
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GSK Biologicals' dTpa vaccine has recently been approved by the US Food and Drug Administration (FDA) for booster vaccination of adolescents aged 10 to 18 years. The ACIP has recently issued provisional recommendations for universal adult Tdap vaccination. The current study will provide pivotal data in support of extending the age range for Boostrix vaccine to include adults 19-64 years of age.

Official Title
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A Study to Evaluate Immunogenicity and Safety of Boostrix Compared to Adacel When Administered as a Booster Vaccination in Adults Aged 19 to 64 Years of Age

Conditions
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Acellular Pertussis, Diphtheria, Tetanus

Intervention / Treatment
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* Biological: Boostrix™
* Biological: ADACEL®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A healthy male or female, 19 to 64 years of age (not having reached the 65th birthday) at the time of study vaccination. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding administration of study vaccine, or planned use during the active phase of the study. Chronic administration of immunosuppressants or within six months prior to administration of study vaccine. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of administration of study vaccine (with the exception of an influenza vaccine). Administration of a diphtheria-tetanus (Td) booster within previous five years. Administration of Tdap vaccine at any time prior to study entry. History of serious allergic reaction (e.g. anaphylaxis) following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine or any component of the study vaccines.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 64 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 Group<br>Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Boostrix® vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0. | Biological: Boostrix™<br>* Combined Reduced Antigen Content Diphtheria, Tetanus, Acellular Pertussis Vaccine<br>|
| Experimental: Adacel Group<br>Subjects, male or female, between, and including, 19 and 64 years of age received a single dose of Adacel™ vaccine administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0. | Biological: ADACEL®<br>* Sanofi Pasteur<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies | A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to ( ≥) 0.1 international units per milliliter (IU/mL). | At Month 1 | 
| Number of Seropositive Subjects With Anti-tetanus (Anti-T) Antibodies | A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL). | At Month 1 | 
| Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Month 1 | 
| Number of Subjects With Booster Responses for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Booster responses for anti-PT, anti-FHA and anti-PRN antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 5 EU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥) 20 EU/mL), one month after vaccination; for initially seropositive subjects with pre-vaccination concentration ≥ 5 EU/mL and < 20 EU/mL: an increase in antibody concentrations of at least four times the pre-vaccination concentration one month after vaccination; and for initially seropositive subjects with pre-vaccination concentration ≥ 20 EU/mL: an increase in antibody concentrations of at least two times the pre-vaccination concentration, one month after vaccination. | At Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects With Anti-diphteria (Anti-D) Antibodies | A seropositive subject was a subject whose antibody concentration was greater than or equal to the cut-off value. Cut-off values assessed were greater than or equal to (≥) 1.0 international units per milliliter (IU/mL). | At Month 1 | 
| Number of Subjects With Booster Responses for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) | Booster responses for anti-D and anti-T antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below cut-off: smaller than (<) 0.1 IU/mL): antibody concentrations at least four times the cut-off (post-vaccination concentration greater than or equal to (≥ 0.4 IU/mL), one month after vaccination; and 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. | At Month 1 | 
| Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) 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 | 
| 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. | During the 15-day period (Day 0-14) following vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, fever [defined as temperature measured orally, greater than or equal to (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [gastro sympt.] and headache. Any = occurrence of the symptom regardless of intensity grade. 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. | During the 15-day period (Day 0-14) following vaccination | 
| 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 (Days 0-30) following vaccination | 
| 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 active phase of the study (Day 0 - Day 30) | 
| 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 extended safety follow-up (ESFU) phase (Day 31 - Month 6) | 
| Number of Subjects Reporting Hospitalizations | Hospitalization signified that the subject had been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out patient setting. | During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) | 
| Number of Subjects Reporting Emergency Room Visits | Emergency room visits refer to AEs requiring immediate medical attention. | During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) | 
| Number of Subjects Reporting the Onset of New Chronic Illnesses | New onset chronic illnesses include diabetes, asthma, allergies, autoimmune diseases. | During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylaxis for diphtheria, tetanus, pertussis, Immunogenicity, booster, dTpa