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

• ClinicalTrials.gov Identifier: NCT00346073
• Recruitment Status: Completed
• First Posted: June 29, 2006
• Results First Posted: August 7, 2018
• Last Update Posted: August 7, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acellular Pertussis; Diphtheria; Tetanus	Biological: Boostrix™; Biological: ADACEL®	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: July 13, 2006
• Actual Primary Completion Date: March 1, 2007
• Actual Study Completion Date: March 7, 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Boostrix Group; 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™; Combined Reduced Antigen Content Diphtheria, Tetanus, Acellular Pertussis Vaccine
Experimental: Adacel Group; 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®; Sanofi Pasteur

Outcome Measures

Primary Outcome Measures :

1. Number of Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Month 1 ]
   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).
2. Number of Seropositive Subjects With Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Month 1 ]
   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).
3. Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Month 1 ]
   Concentrations are presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
4. Number of Subjects With Booster Responses for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies [ Time Frame: At Month 1 ]
   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.

Secondary Outcome Measures :

1. Number of Seropositive Subjects With Anti-diphteria (Anti-D) Antibodies [ Time Frame: At Month 1 ]
   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).
2. Number of Subjects With Booster Responses for Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) [ Time Frame: At Month 1 ]
   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.
3. Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Month 1 ]
   Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
4. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 15-day period (Day 0-14) following vaccination ]
   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.
5. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 15-day period (Day 0-14) following vaccination ]
   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.
6. Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: During the 31-day period (Days 0-30) following vaccination ]
   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.
7. Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: During the active phase of the study (Day 0 - Day 30) ]
   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.
8. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the extended safety follow-up (ESFU) phase (Day 31 - Month 6) ]
   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.
9. Number of Subjects Reporting Hospitalizations [ Time Frame: During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) ]
   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.
10. Number of Subjects Reporting Emergency Room Visits [ Time Frame: During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) ]
    Emergency room visits refer to AEs requiring immediate medical attention.
11. Number of Subjects Reporting the Onset of New Chronic Illnesses [ Time Frame: During the extended safety follow-up (ESFU) period (from Day 31 to Month 6) ]
    New onset chronic illnesses include diabetes, asthma, allergies, autoimmune diseases.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Huntsville, Alabama, United States, 35802

United States, Arizona

GSK Investigational Site

Chandler, Arizona, United States, 85224

GSK Investigational Site

Mesa, Arizona, United States, 85203

GSK Investigational Site

Mesa, Arizona, United States, 85213

GSK Investigational Site

Peoria, Arizona, United States, 85381 - 4828

GSK Investigational Site

Phoenix, Arizona, United States, 85014

GSK Investigational Site

Tempe, Arizona, United States, 85283

United States, Arkansas

GSK Investigational Site

Little Rock, Arkansas, United States, 72205

United States, California

GSK Investigational Site

San Diego, California, United States, 92103-6204

GSK Investigational Site

San Diego, California, United States, 92108

United States, Colorado

GSK Investigational Site

Colorado Springs, Colorado, United States, 80909

GSK Investigational Site

Pueblo, Colorado, United States, 81001

United States, District of Columbia

GSK Investigational Site

Washington, District of Columbia, United States, 20036

United States, Florida

GSK Investigational Site

Melbourne, Florida, United States, 32901

GSK Investigational Site

Miami, Florida, United States, 33143

GSK Investigational Site

Pembroke Pines, Florida, United States, 33024

GSK Investigational Site

Tampa, Florida, United States, 33603

United States, Idaho

GSK Investigational Site

Boise, Idaho, United States, 83713

United States, Illinois

GSK Investigational Site

Peoria, Illinois, United States, 61602

United States, Indiana

GSK Investigational Site

South Bend, Indiana, United States, 46601

United States, Kentucky

GSK Investigational Site

Bardstown, Kentucky, United States, 40004

United States, Michigan

GSK Investigational Site

Richland, Michigan, United States, 49083

United States, Missouri

GSK Investigational Site

Kansas City, Missouri, United States, 64114

GSK Investigational Site

Saint Louis, Missouri, United States, 63141

United States, Nebraska

GSK Investigational Site

Alliance, Nebraska, United States, 69301

GSK Investigational Site

North Platte, Nebraska, United States, 69101

United States, Nevada

GSK Investigational Site

Las Vegas, Nevada, United States, 89104

United States, New Mexico

GSK Investigational Site

Albuquerque, New Mexico, United States, 87108

United States, North Carolina

GSK Investigational Site

Hickory, North Carolina, United States, 28601

GSK Investigational Site

Raleigh, North Carolina, United States, 27609

GSK Investigational Site

Winston-Salem, North Carolina, United States, 27103

United States, North Dakota

GSK Investigational Site

Bismarck, North Dakota, United States, 58501

United States, Oklahoma

GSK Investigational Site

Oklahoma City, Oklahoma, United States, 73112

United States, Pennsylvania

GSK Investigational Site

Grove City, Pennsylvania, United States, 16127

GSK Investigational Site

Pittsburgh, Pennsylvania, United States, 15241

United States, Tennessee

GSK Investigational Site

Bristol, Tennessee, United States, 37620

GSK Investigational Site

Knoxville, Tennessee, United States, 37920

United States, Texas

GSK Investigational Site

Houston, Texas, United States, 77024

United States, Utah

GSK Investigational Site

Salt Lake City, Utah, United States, 84109

GSK Investigational Site

Salt Lake City, Utah, United States, 84121

GSK Investigational Site

West Jordan, Utah, United States, 84088

United States, Virginia

GSK Investigational Site

Norfolk, Virginia, United States, 23507

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Study Protocol 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 106316
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

Blatter M, Friedland LR, Weston WM, Li P, Howe B. Immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19-64 years of age. Vaccine. 2009 Jan 29;27(5):765-72. doi: 10.1016/j.vaccine.2008.11.028. Epub 2008 Nov 27.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00346073
• Other Study ID Numbers: 106316
• First Posted: June 29, 2006
• Results First Posted: August 7, 2018
• Last Update Posted: August 7, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

Prophylaxis for diphtheria, tetanus, pertussis; Immunogenicity, booster, dTpa

Additional relevant MeSH terms:

Whooping Cough; Tetanus; Diphtheria; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Respiratory Tract Infections; Infection; Respiratory Tract Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Corynebacterium Infections; Actinomycetales Infections