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US-licensed Combined Vaccine Against Tetanus & Diphtheria, Given With US-licensed Vaccine Against Meningococcal Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00282295
First received: January 25, 2006
Last updated: January 23, 2017
Last verified: January 2017
  Purpose
New immunization recommendations in the US include vaccination of adolescents against pertussis and meningococcal disease. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that Tdap (Tetanus Toxoid, Reduced Diphtheria Toxoid And Acellular Pertussis Vaccine Adsorbed) and MCV4 (Meningococcal conjugate vaccine against serotypes A, C, Y and W-135) vaccines be administered to adolescents at the same office visit if vaccination with both vaccines is indicated. Therefore, this study is designed to evaluate the safety and immunogenicity of a booster vaccination with Boostrix co-administered with Menactra as compared to the administration of either vaccine alone in healthy adolescents 11 - 18 years of age.

Condition Intervention Phase
Acellular Pertussis
Tetanus
Diphtheria
Biological: Boostrix®
Biological: Menactra™
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant
Primary Purpose: Prevention
Official Title: Safety & Immunogenicity of a Booster Dose of dTPa Vaccine (Boostrix®) Co-admnd. With Aventis Pasteur's Meningococcal (Serogroups A, C, Y and W-135) Polysaccharide Vaccine (Menactra™) vs Admn. of Either Vaccine Alone in Healthy Adolescents

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Month 1 (post Boostrix® vaccination) ]
    Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).

  • Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Month 1 (post Boostrix® vaccination) ]
    Concentrations were presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

  • 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 (post Boostrix® vaccination) ]

    Booster responses for anti-PT, anti-FHA and anti-PRN antibodies were defined as:

    for initially seronegative subjects (pre-vaccination concentration below the cut-off concentration of 5 EL.U/mL): antibody concentrations at least four times the cut-off (postvaccination concentration ≥ 20 EL.U/mL) one month after vaccination with the Boostrix® vaccine; 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 the Boostrix® vaccine; and 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 the Boostrix® vaccine.


  • Number of Subjects With Vaccine Responses for Serum Bactericidal Assay Against Neisseria Meningitidis Serogroups A (rSBA-MenA), C (rSBA-MenC), Y (rSBA-MenY) and W-135 (rSBA-MenW-135) [ Time Frame: At Month 1 (post Boostrix® vaccination) ]
    Vaccine responses for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below the cut-off titer of 8): antibody titers at least four times the cut-off (post-vaccination concentration ≥ 32) one month after vaccination with Menactra™ vaccination; and for initially seropositive subjects (pre-vaccination titer ≥ 8): antibody titers at least four times the pre-vaccination antibody titers, one month after vaccination with Menactra™ vaccine.


Secondary Outcome Measures:
  • Number of Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Day 0 (PRE) before Boostrix® vaccination ]
    Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).

  • Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Month 1 (post Boostrix® vaccination) ]
    Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).

  • Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens [ Time Frame: At Day 0 (PRE) and at Month 1 (M1) post Boostrix® vaccination ]
    Cut-off values assessed were greater than or equal to 0.1 international units per milliliter (IU/m L).

  • Number of Subjects With Booster Responses for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies [ Time Frame: At Month 1 (post Boostrix® vaccination) ]

    Booster responses for anti-D and anti-T antibodies were defined as:

    for initially seronegative subjects (pre-vaccination concentration below the cut-off concentration of 0.1 IU/mL): antibody concentrations at least four times the cut-off (postvaccination concentration ≥ 0.4 IU/mL), one month after vaccination with the Boostrix® vaccine; 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 with the Boostrix® vaccine.


  • Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Day 0 (PRE) and at Month 1 (M1) post Boostrix® vaccination ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).

  • Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Month 1 (M1) post Menactra™ vaccination ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).

  • 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 Month1 (post Boostrix® vaccination) ]
    Booster responses for anti-PT, anti-FHA and anti-PRN antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below the cut-off concentration of 5 EL.U/mL): antibody concentrations at least four times the cut-off (postvaccination concentration ≥20 EL.U/mL) one month after vaccination with the Boostrix® vaccine; 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 the Boostrix® vaccine; and 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 the Boostrix® vaccine.

  • Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Day 0 before (PRE) Boostrix® vaccination ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).

  • Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Month 1 (post Boostrix® vaccination) ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).

  • Titers for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 Antibodies [ Time Frame: At Day 0 (PRE) and at Month 1 (M1) post Menactra™ vaccination ]
    Antibody titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Vaccine Responses for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 Antibodies [ Time Frame: At Month 1 (one month after vaccination with Menactra™ vaccine) ]
    Vaccine responses for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 antibodies were defined as: for initially seronegative subjects (pre-vaccination concentration below the cut-off titer of 8): antibody titers at least four times the cut-off (post-vaccination concentration ≥ 32) one month after vaccination with Menactra™ the vaccine, and for initially seropositive subjects (pre-vaccination titer ≥ 8): antibody titers at least four times the pre-vaccination antibody titers, one month after vaccination with the Menactra™ vaccine.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: Within 4-days (Day 0-3) after each dose and across doses ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = any solicited local symptom irrespective of intensity grade. Grade 3 pain = pain that prevented normal activities. Grade 3 redness/swelling = redness/swelling with diameter ≥ 50 millimeters (mm).

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: Within 4-days (Days 0-3) after each dose and across doses ]
    Assessed solicited general symptoms were fatigue, fever [defined as oral temperature equal to or above 37.5 degrees Celsius (°C)], headache and gastrointestinal symptoms [gastro sympt]. Any = any solicited general symptom irrespective of intensity grade or relationship to vaccination. Grade 3 = symptoms that prevented normal activities. Grade 3 Fever = temperature higher than (>) 39° C. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: Within the 31-day (Days 0-30) period after each 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. Grade 3 AE =An AE which prevented normal, everyday activities. Such an AE, for example, prevented attendance at work/school and necessitated the administration of corrective therapy. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period (Day 0 - Month 2) ]
    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.


Enrollment: 1376
Study Start Date: January 2006
Study Completion Date: August 2006
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Boostrix + Menactra Group
Subjects, 11 through 18 years of age, received a booster dose of Boostrix® co-administered with Menactra™ at Day 0. The Boostrix® vaccine was administered intramuscularly into the left deltoid region and Menactra™ vaccine was administered intramuscularly into the right deltoid region.
Biological: Boostrix®
GlaxoSmithKline (GSK) Biologicals' registered tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.
Biological: Menactra™
Aventis Pasteur's me ningococcal polysaccharide diphtheria toxoid conjugate vaccine containing Neisseria meningitidis serogroups, A, C, Y and W-135.
Experimental: Boostrix-Menactra Group
Subjects, 11 through 18 years of age, received one dose of Boostrix® vaccine at Day 0, followed by one dose of Menactra™ vaccine at Month 1. Both vaccines were administered intramuscularly into the left deltoid region.
Biological: Boostrix®
GlaxoSmithKline (GSK) Biologicals' registered tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.
Biological: Menactra™
Aventis Pasteur's me ningococcal polysaccharide diphtheria toxoid conjugate vaccine containing Neisseria meningitidis serogroups, A, C, Y and W-135.
Experimental: Menactra-Boostrix Group
Subjects, 11 through 18 years of age, received one dose of Menactra™ vaccine at Day 0 followed by one dose of Boostrix® vaccine at Month 1. Both vaccines were administered intramuscularly into the left deltoid region.
Biological: Boostrix®
GlaxoSmithKline (GSK) Biologicals' registered tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.
Biological: Menactra™
Aventis Pasteur's me ningococcal polysaccharide diphtheria toxoid conjugate vaccine containing Neisseria meningitidis serogroups, A, C, Y and W-135.

Detailed Description:

A phase IV, randomized, partially blinded multicenter study to evaluate the safety and immunogenicity of a booster vaccination with GlaxoSmithKline's tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed [Tdap Boostrix®] co-administered intramuscularly with Aventis-Pasteur's meningococcal (serogroups A, C, Y and W-135) polysaccharide diphtheria toxoid conjugate vaccine (Menactra™) as compared to the administration of either vaccine alone in healthy adolescents 11-18 years of age. "Experimental design: Prospective, randomized, controlled multicenter study with three groups:

Group 1: Boostrix + Menactra on Day 0, blood samples at Month 0 and Month 1 Group 2: Boostrix on Day 0, Menactra at Month 1, blood samples at Month 0, Month 1, and Month 2 Group 3: Menactra on Day 0, Boostrix at Month 1, blood samples at Month 0, Month 1 and Month 2 Treatment allocation: randomized 1:1:1 Type of study: self-contained Duration of the study: Approximately one month for each subject in Group 1 and approximately two months for each subject in the Group 2 and Group 3."

  Eligibility

Ages Eligible for Study:   11 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy subjects as established by medical history and history-directed physical examination before entering into the study.
  • Previously completed routine childhood vaccinations against diphtheria, tetanus and pertussis diseases according to the recommended vaccination schedule at the time.
  • Females of childbearing potential at the time of study entry are required to have a negative pregnancy test prior to administration of the dose of vaccine and are required to be abstinent or use adequate contraceptive precautions for one month prior to vaccination. Subjects also are required to agree to continue such precautions for two months after vaccination.

Exclusion Criteria:

  • Administration of a pre-school booster of DTP vaccine within the previous 5 years
  • Administration of a diphteria-tetanus (Td) booster within the previous 5 years
  • Previous vaccination against N. meningitidis
  • Hypersensitivity to latex
  • History of serious allergic reaction (e.g. anaphylaxis) following any other tetanus toxoid, diphteria toxoid or pertussis-containing vaccine or any component of the study vaccines
  • History of encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) within seven days of administration of a previous dose of pertussis vaccine taht is not attributable to another identifiable cause
  • Progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy: pertussis vaccine should not be administered to individuals with these conditions until a treatment regimen has been established and the condition has stabilized
  • Previous history of Guillain-Barré syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282295

  Show 24 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Friedland et al. Immunogenicity of coadministered Tdap and MCV4 vaccines compared to separately administered vaccines. Accepted for poster presentation at ICAAC 2007
Weston et al. Reactogenicity of concomitant and separately administered Tdap and MCV4 vaccines. Accepted for poster presentation at ICAAC 2007

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 105753
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00282295     History of Changes
Other Study ID Numbers: 105753
Study First Received: January 25, 2006
Results First Received: January 23, 2017
Last Updated: January 23, 2017
Individual Participant Data  
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:
tetanus
pertussis
Prophylaxis
meningococcus
diptheria

Additional relevant MeSH terms:
Whooping Cough
Tetanus
Tetany
Diphtheria
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases
Clostridium Infections
Gram-Positive Bacterial Infections
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Hypocalcemia
Calcium Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Corynebacterium Infections
Actinomycetales Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 28, 2017