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

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
Haemophilus Influenzae Type b Disease Pneumococcal Disease Hepatitis B Disease Persistence of Immunogenicity Meningococcal Disease	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:

MedlinePlus related topics: Flu Hepatitis Hepatitis A Hepatitis B Meningococcal Infections

Drug Information available for: Heptavalent pneumococcal conjugate vaccine Pneumococcal Vaccines

U.S. FDA Resources

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.
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 ]
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.

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 ≥ 0.15 microgram per milliliter (μg/mL) and ≥ 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 booster 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
Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
rSBA-MenC Titers [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
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 ]
Anti-PRP Concentrations [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
Antibody Concentrations Against Vaccine Pneumococcal Serotypes [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
Number of Subjects With Opsonophagocytic Activity [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
Concentration of Antibodies Against Protein D [ Time Frame: At 6 years of age ] [ Designated as safety issue: No ]
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 booster study (NCT00463437) at 17-24 months of age until 6 years of age ] [ Designated as safety issue: No ]
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.
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 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 ≥ 0.15 microgram per milliliter (μg/mL) and ≥ 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 booster 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

Enrollment:	582
Study Start Date:	May 2009
Estimated Study Completion Date:	December 2012
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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. 3 primary doses of Pediarix 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 Pediarix.	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. 3 primary doses of Pediarix 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 Pediarix.	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
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. 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

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

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, 14197
GSK Investigational Site
Berlin, Germany, 13355
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:	November 21, 2012
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:

Hepatitis
Hepatitis A
Hepatitis B
Influenza, Human
Meningococcal Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections

Hepadnaviridae Infections
DNA Virus Infections
Orthomyxoviridae Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013