Persistence of Antibodies at 3, 4 and 6 Years of Age After Vaccination With Meningococcal, Pneumococcal and Hib Vaccines

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00891176
First received: April 30, 2009
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

This protocol posting deals with objectives & outcome measures of an extension phase when subjects are aged 3, 4 and 6 years of age. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00334334). The objectives & outcome measures of the booster phase are presented in a separate protocol posting (NCT number = NCT00463437).

The purpose of this study is to evaluate the persistence of pneumococcal, meningococcal serogroup C, Hib and Hepatits B antibodies after booster vaccination, when the subjects are aged 3, 4 and 6 years. No vaccine will be administered during this persistence phase of the study.


Condition Intervention Phase
Neisseria Meningitidis
Haemophilus Influenzae Type b
Biological: MenitorixTM
Biological: Pneumococcal conjugate vaccine GSK1024850A
Biological: PrevenarTM
Biological: MeningitecTM
Biological: NeisVac-CTM
Biological: InfanrixTM hexa
Biological: InfanrixTM penta
Biological: InfanrixTM IPV/Hib
Biological: InfanrixTM IPV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Persistence of Antibodies After Full Vaccination Course With GSK Biologicals' Menitorix or MenC Conjugate Vaccine, Co-administered With DTPa or DTPa/Hib Containing Vaccine and Pneumococcal Conjugate Vaccine, in Children up to 6 Years of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.

  • Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off value assessed was equal to or above 1:8. The rSBA-MenC assay was performed at the Public Health England (PHE) laboratory at 6 years of age while the GSK laboratory was used for testing at 3 and 4 years of age.


Secondary Outcome Measures:
  • Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    The cut-off value was defined as a titer equal to or above 1:128.

  • rSBA-MenC Titers [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs).

  • Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    The cut-off values were defined as a concentration equal to or above 0.15 microgram per milliliter (μg/mL) and equal to or above 1.0 μg/mL.

  • Anti-PRP Concentrations [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL,

  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]

    Antibody concentrations were expressed as GMCs in μg/mL.

    Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.


  • Number of Subjects With Opsonophagocytic Activity [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Opsonophagocytic activity was measured by a killing-assay. The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titre of 8.

  • Concentration of Antibodies Against Protein D [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Cut-off values assessed were defined as equal to or above 10 milli-international units per milliliter (mIU/mL) or equal to or above 100 mIU/mL.

  • Anti-HBs Antibody Concentrations [ Time Frame: At 3 years of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as GMCs in mIU/mL.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From last study contact of the study (NCT00463437) at 17-24 months of age until 3 years of age ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related = SAE assessed by the investigator as being related to the study procedures.

  • rSBA-MenC Titers [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs).

  • Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.

  • Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    The cut-off values were defined as a concentration equal to or above 0.15 microgram per milliliter (μg/mL) and equal to or above 1.0 μg/mL.

  • Anti-PRP Concentrations [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL

  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Antibody concentrations were expressed as GMCs in μg/mL. Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Number of Subjects With Opsonophagocytic Activity [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Opsonophagocytic activity was measured by a killing-assay. The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer of 8.

  • Concentration of Antibodies Against Protein D [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Cut-off values assessed were defined as equal to or above 10 milli-international units per milliliter (mIU/mL) or equal to or above 100 mIU/mL.

  • Anti-HBs Antibody Concentrations [ Time Frame: At 4 years of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as GMCs in mIU/mL.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From last study contact of the study (NCT00463437) at 17-24 months of age until 4 years of age ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related = SAE assessed by the investigator as being related to the study procedures.

  • Number of Subjects With rSBA-MenC Titer Equal to or Above Cut-off Value [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.

  • rSBA-MenC Titers [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs).

  • Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    The cut-off values were defined as a concentration ≥ 0.15 microgram per milliliter (μg/mL) and ≥ 1.0 μg/mL.

  • Anti-PRP Concentrations [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    Concentrations were defined as Geometric Mean Concentrations (GMCs) in μg/mL

  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    Antibody concentrations were expressed as GMCs in μg/mL. Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Number of Subjects With Opsonophagocytic Activity [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    Opsonophagocytic activity was measured by a killing-assay. The results were presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer of 8.

  • Concentration of Antibodies Against Protein D [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
  • Anti-HBs Antibody Concentrations [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From last study contact of the study (NCT00463437) at 17-24 months of age until 6 years of age ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Related = SAE assessed by the investigator as being related to the study procedures.


Enrollment: 582
Study Start Date: May 2009
Study Completion Date: November 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Synflorix-Meningitec Group
Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age 2 primary doses of Meningitec intramuscularly into the lower left thigh at 2 and 4 months of age. 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Meningitec at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.
Biological: Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: MeningitecTM
Intramuscular injection into the thigh as primary vaccination at 2 and 4 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study
Biological: InfanrixTM hexa
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (all countries) and as booster dose at 11-18 months of age (Germany and Poland). No vaccine was administered during this long-term follow up study
Biological: InfanrixTM IPV/Hib
Intramuscular injection into the thigh as booster dose at 11-18 months of age (Spain). No vaccine was administered during this long-term follow up study
Experimental: Synflorix-NeisVac-C Group
Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 2 primary doses of Neis-Vac-C intramuscularly into the lower left thigh at 2 and 4 months of age and 3 primary doses of Infanrix hexa intramuscularly into the upper left thigh at 2, 4 and 6 months of age. (In Poland subjects were offered a third dose of Neis-Vac-C at 7 months of age to comply with national recommendations). During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV/Hib was given instead of Infanrix hexa.
Biological: Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: NeisVac-CTM
Intramuscular injection into the thigh as primary vaccination at 2 and 4 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study
Biological: InfanrixTM hexa
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (all countries) and as booster dose at 11-18 months of age (Germany and Poland). No vaccine was administered during this long-term follow up study
Biological: InfanrixTM IPV/Hib
Intramuscular injection into the thigh as booster dose at 11-18 months of age (Spain). No vaccine was administered during this long-term follow up study
Experimental: Synflorix-Menitorix Group
Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Synflorix intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Biological: MenitorixTM
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: InfanrixTM penta
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (all countries) and as booster dose at 11-18 months of age (Germany and Poland). No vaccine was administered during this long-term follow up study
Biological: InfanrixTM IPV
Intramuscular injection into the thigh as booster dose at 11-18 months of age (Spain). No vaccine was administered during this long-term follow up study
Active Comparator: Prevenar-Menitorix Group
Subjects who received concomitantly in the primary study (NCT00334334): 3 primary doses of Prevenar intramuscularly into the right thigh at 2, 4 and 6 months of age, 3 primary doses of Menitorix intramuscularly into the lower left thigh at 2, 4 and 6 months of age and 3 primary doses of Infanrix penta intramuscularly into the upper left thigh at 2, 4 and 6 months of age. During the booster study (NCT00463437) subjects received the same vaccines as during the primary study at 11-18 months of age, with the exception of Spain, where Infanrix IPV was given instead of Infanrix penta.
Biological: MenitorixTM
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: Pneumococcal conjugate vaccine GSK1024850A
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: PrevenarTM
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age and as booster dose at 11-18 months of age. No vaccine was administered during this long-term follow up study.
Biological: InfanrixTM penta
Intramuscular injection into the thigh as primary vaccination at 2, 4 and 6 months of age (all countries) and as booster dose at 11-18 months of age (Germany and Poland). No vaccine was administered during this long-term follow up study
Biological: InfanrixTM IPV
Intramuscular injection into the thigh as booster dose at 11-18 months of age (Spain). No vaccine was administered during this long-term follow up study

Detailed Description:

This multicenter study is open. No vaccine will be administered during this persistence phase of the study. The subjects were randomized in the primary vaccination study 107005 and will not be further randomized in this study.

  Eligibility

Ages Eligible for Study:   36 Months to 76 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female between, and including, 36 and 40 months of age at the time of Visit 1; between, and including, 48 and 52 months of age at the time of Visit 2; and between, and including, 72 and 76 months of age at the time of Visit 3.
  • Written informed consent obtained from the parent or guardian of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Subjects who previously participated in the primary and booster studies, who received a full vaccination course with the vaccines corresponding to their group during the primary and booster studies and who were part, in the booster study, of the blood sampling subset.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the first blood sampling.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
  • Administration of any additional meningococcal serogroup C, Hib, hepatitis B and pneumococcal vaccine since the end of the booster study
  • History of meningococcal serogroup C, Haemophilus influenzae type b, hepatitis B and invasive pneumococcal diseases since the end of booster study.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition since the end of booster study, based on medical history and physical examination (no laboratory testing required).
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first blood sampling.
  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: NCT00891176

Locations
Germany
GSK Investigational Site
Bad Saulgau, Baden-Wuerttemberg, Germany, 88348
GSK Investigational Site
Bretten, Baden-Wuerttemberg, Germany, 75015
GSK Investigational Site
Ettenheim, Baden-Wuerttemberg, Germany, 77955
GSK Investigational Site
Karlsruhe, Baden-Wuerttemberg, Germany, 76189
GSK Investigational Site
Kehl, Baden-Wuerttemberg, Germany, 77694
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68163
GSK Investigational Site
Oberstenfeld, Baden-Wuerttemberg, Germany, 71720
GSK Investigational Site
Schwaebisch-Hall, Baden-Wuerttemberg, Germany, 74523
GSK Investigational Site
Tettnang, Baden-Wuerttemberg, Germany, 88069
GSK Investigational Site
Muenchen, Bayern, Germany, 81735
GSK Investigational Site
Muenchen, Bayern, Germany, 81675
GSK Investigational Site
Noerdlingen, Bayern, Germany, 86720
GSK Investigational Site
Hille, Nordrhein-Westfalen, Germany, 32479
GSK Investigational Site
Loehne, Nordrhein-Westfalen, Germany, 32584
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48163
GSK Investigational Site
Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
GSK Investigational Site
Frankenthal, Rheinland-Pfalz, Germany, 67227
GSK Investigational Site
Trier, Rheinland-Pfalz, Germany, 54290
GSK Investigational Site
Doebeln, Sachsen, Germany, 04720
GSK Investigational Site
Lobenstein, Thueringen, Germany, 07356
GSK Investigational Site
Weimar, Thueringen, Germany, 99425
GSK Investigational Site
Berlin, Germany, 13355
GSK Investigational Site
Berlin, Germany, 14197
Poland
GSK Investigational Site
Debica, Poland, 39-200
GSK Investigational Site
Krakow, Poland
GSK Investigational Site
Siemianowice Slaskie, Poland, 41-103
Spain
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Móstoles/Madrid, Spain, 28935
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00891176     History of Changes
Other Study ID Numbers: 112830
Study First Received: April 30, 2009
Results First Received: November 30, 2010
Last Updated: February 13, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
Poland: Centralna Ewidencja Badań Klinicznych Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Germany: Paul-Ehrlich-Institut

Keywords provided by GlaxoSmithKline:
Conjugate vaccines
Meningococcal serogroup C vaccine
Antibody persistence
Pneumococcal vaccine
Haemophilus Influenzae type b vaccine

Additional relevant MeSH terms:
Antibodies
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014