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

Tetanus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282295
• Other study ID #: 105753
• Status: Completed
• Phase: Phase 4
• Start date: January 25, 2006
• Est. completion date: August 8, 2006

Study information

• Verified date: June 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1344
• Est. completion date: August 8, 2006
• Est. primary completion date: August 8, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 11 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Acellular Pertussis
• Diphtheria
• Tetanus
• Whooping Cough

Intervention

Biological:
• Boostrix®
GlaxoSmithKline (GSK) Biologicals' registered tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed, containing 0.3 mg aluminum.
• Menactra™
Aventis Pasteur's me ningococcal polysaccharide diphtheria toxoid conjugate vaccine containing Neisseria meningitidis serogroups, A, C, Y and W-135.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Akron	Ohio
United States	GSK Investigational Site	Annapolis	Maryland
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Frederick	Maryland
United States	GSK Investigational Site	Golden	Colorado
United States	GSK Investigational Site	Greenville	Pennsylvania
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsford	New York
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	University Heights	Ohio
United States	GSK Investigational Site	West Jordan	Utah
United States	GSK Investigational Site	Whitehouse Station	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (2)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies	Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).	At Month 1 (post Boostrix vaccination)
Primary	Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations	Concentrations were presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	At Month 1 (post Boostrix vaccination)
Primary	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 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.	At Month 1 (post Boostrix vaccination)
Primary	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)	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.	One month post Boostrix vaccination ((Month 1 for Boostrix + Menactra Group and Month 2 for Menactra-Boostrix Group)
Secondary	Number of Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies	Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).	At Day 0 (PRE) before Boostrix vaccination
Secondary	Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies	Cut-off values assessed were greater than or equal to 1.0 international units per milliliter (IU/mL).	At Month 2 (one month post Boostrix vaccination)
Secondary	Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens	Cut-off values assessed were greater than or equal to 0.1 international units per milliliter (IU/m L).	PRE (Day 0) and POST Boostrix vaccination (Month 1 for Boostrix + Menactra Group and Boostrix-Menactra Group/ Month 2 for Menactra-Boostrix Group)
Secondary	Number of Subjects With Booster Responses for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies	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.	At one month POST Boostrix vaccination (Month 1 for Boostrix + Menactra Group and Boostrix-Menactra Group/ Month 2 for Menactra-Boostrix Group)
Secondary	Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).	PRE (Day 0) and one month POST Boostrix vaccination (Month 1 for Boostrix + Menactra Group and Boostrix-Menactra Group/ Month 2 for Menactra-Boostrix Group)
Secondary	Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).	At one month POST Menactra vaccination (Month 2 for Boostrix-Menactra Group and Month 1 for Menactra-Boostrix Group)
Secondary	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 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.	At Month 2 (one month post Boostrix vaccination)
Secondary	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), expressed in ELISA units per milliliter (EL.U/mL).	At Day 0 before (PRE) Boostrix vaccination
Secondary	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), expressed in ELISA units per milliliter (EL.U/mL).	At Month 2 (one month post Boostrix vaccination)
Secondary	Titers for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 Antibodies	Antibody titers are presented as geometric mean titers (GMTs).	PRE (Day 0) and one month POST Menactra vaccination (Month 2 for Boostrix + Menactra Group and Boostrix-Menactra Group / Month 1 for Menactra-Boostrix Group)
Secondary	Number of Subjects With Vaccine Responses for rSBA-MenA, rSBA-MenC, rSBA-MenY and rSBA-MenW-135 Antibodies	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.	At Month 2 (one month after vaccination with Menactra vaccine)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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).	Within 4-days (Day 0-3) after each dose and across doses
Secondary	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)], 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.	Within 4-days (Days 0-3) after each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related 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. 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.	Within the 31-day (Days 0-30) period after each vaccination
Secondary	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.	Throughout the entire study period (Day 0 - Month 2)

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