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

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

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.

Study Overview

• Status: Completed
• Conditions: Tetanus; Diphtheria; Acellular Pertussis
• Intervention / Treatment: Biological: Fluarix®; Biological: Boostrix®

• Study Type: Interventional
• Enrollment (Actual): 1726
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • GSK Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • GSK Investigational Site
    • Mesa, Arizona, United States, 85213
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85014
      • GSK Investigational Site
  • Florida
    • Inverness, Florida, United States, 34452
      • GSK Investigational Site
    • Melbourne, Florida, United States, 32935
      • GSK Investigational Site
    • Pembroke Pines, Florida, United States, 33024
      • GSK Investigational Site
  • Illinois
    • Peoria, Illinois, United States, 61602
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15217
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15220
      • GSK Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77024
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BOOSTRIX+FLUARIX GROUP; 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®; GSK Biologicals' inactivated influenza split virus vaccine.; Biological: Boostrix®; GSK Biologicals' tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.
Experimental: FLUARIX BOOSTRIX GROUP; 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®; GSK Biologicals' inactivated influenza split virus vaccine.; Biological: Boostrix®; GSK Biologicals' tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Weston WM, Friedland LR, Wu X, Howe B. Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix((R))): results of two randomized trials. Vaccine. 2012 Feb 21;30(9):1721-8. doi: 10.1016/j.vaccine.2011.12.055. Epub 2011 Dec 31.
• Weston WM, Chandrashekar V, Friedland LR, Howe B. Safety and immunogenicity of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine when co-administered with influenza vaccine in adults. Hum Vaccin. 2009 Dec;5(12):858-66. doi: 10.4161/hv.9961. Epub 2009 Dec 31.

Helpful Links

• 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 record dates

Study Major Dates

• Study Start (Actual): October 23, 2006
• Primary Completion (Actual): February 28, 2007
• Study Completion (Actual): February 28, 2007

Study Registration Dates

• First Submitted: October 6, 2006
• First Submitted That Met QC Criteria: October 6, 2006
• First Posted (Estimate): October 9, 2006

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: June 6, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Influenza; Immunogenicity,; Co-administration,; Tdap,
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Diphtheria
• Other Study ID Numbers: 106323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 106323
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register