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

Haemophilus Influenzae Type b Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00891176
• Other study ID #: 112830
• Status: Completed
• Phase: Phase 3
• First received: April 30, 2009
• Last updated: August 22, 2017
• Start date: May 14, 2009
• Est. completion date: November 21, 2012

Study information

• Verified date: September 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 582
• Est. completion date: November 21, 2012
• Est. primary completion date: November 21, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 36 Months to 76 Months

Eligibility

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.

Related Conditions & MeSH terms

• Haemophilus Influenzae Type b
• Neisseria Meningitidis

Intervention

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.
• 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.
• 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.
• 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
• 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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Bad Saulgau	Baden-Wuerttemberg
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bretten	Baden-Wuerttemberg
Germany	GSK Investigational Site	Doebeln	Sachsen
Germany	GSK Investigational Site	Ettenheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Frankenthal	Rheinland-Pfalz
Germany	GSK Investigational Site	Hille	Nordrhein-Westfalen
Germany	GSK Investigational Site	Karlsruhe	Baden-Wuerttemberg
Germany	GSK Investigational Site	Kehl	Baden-Wuerttemberg
Germany	GSK Investigational Site	Lobenstein	Thueringen
Germany	GSK Investigational Site	Loehne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Noerdlingen	Bayern
Germany	GSK Investigational Site	Oberstenfeld	Baden-Wuerttemberg
Germany	GSK Investigational Site	Porta Westfalica	Nordrhein-Westfalen
Germany	GSK Investigational Site	Schwaebisch-Hall	Baden-Wuerttemberg
Germany	GSK Investigational Site	Tettnang	Baden-Wuerttemberg
Germany	GSK Investigational Site	Trier	Rheinland-Pfalz
Germany	GSK Investigational Site	Weimar	Thueringen
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Siemianowice Slaskie
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Móstoles/Madrid

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	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.	At 3 years of age
Primary	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	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.	At 6 years of age
Primary	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Titers Using Rabbit Complement (rSBA-MenC) Equal to or Above Cut-off Value	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.	At 4 years of age
Secondary	Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value	The cut-off value was defined as a titer equal to or above 1:128.	At 3 years of age
Secondary	rSBA-MenC Titers	Titers are given as Geometric Mean Titers (GMTs).	At 3 years of age
Secondary	Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values	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.	At 3 years of age
Secondary	Anti-PRP Concentrations	Concentrations were defined as Geometric Mean Concentrations (GMCs) in µg/mL,	At 3 years of age
Secondary	Antibody Concentrations Against Vaccine Pneumococcal Serotypes	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.	At 3 years of age
Secondary	Number of Subjects With Opsonophagocytic Activity	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.	At 3 years of age
Secondary	Concentration of Antibodies Against Protein D	Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).	At 3 years of age
Secondary	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values	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.	At 3 years of age
Secondary	Anti-HBs Antibody Concentrations	Concentrations were expressed as GMCs in mIU/mL.	At 3 years of age
Secondary	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, 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.	From last study contact of the study (NCT00463437) at 17-24 months of age until 3 years of age
Secondary	rSBA-MenC Titers	Titers are given as Geometric Mean Titers (GMTs).	At 4 years of age
Secondary	Number of Subjects With an rSBA-MenC Titer Equal to or Above Cut-off Value	rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.	At 4 years of age
Secondary	Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values	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.	At 4 years of age
Secondary	Anti-PRP Concentrations	Concentrations were defined as Geometric Mean Concentrations (GMCs) in µg/mL	At 4 years of age
Secondary	Antibody Concentrations Against Vaccine Pneumococcal Serotypes	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.	At 4 years of age
Secondary	Number of Subjects With Opsonophagocytic Activity	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.	At 4 years of age
Secondary	Concentration of Antibodies Against Protein D	Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).	At 4 years of age
Secondary	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values	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.	At 4 years of age
Secondary	Anti-HBs Antibody Concentrations	Concentrations were expressed as GMCs in mIU/mL.	At 4 years of age
Secondary	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, 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.	From last study contact of the study (NCT00463437) at 17-24 months of age until 4 years of age
Secondary	Number of Subjects With rSBA-MenC Titer Equal to or Above Cut-off Value	rSBA-MenC antibody cut-off value assessed was equal to or above 1:128.	At 6 years of age
Secondary	rSBA-MenC Titers	Titers are given as Geometric Mean Titers (GMTs).	At 6 years of age
Secondary	Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations Equal to or Above Cut-off Values	The cut-off values were defined as a concentration = 0.15 microgram per milliliter (µg/mL) and = 1.0 µg/mL.	At 6 years of age
Secondary	Anti-PRP Concentrations	Concentrations were defined as Geometric Mean Concentrations (GMCs) in µg/mL	At 6 years of age
Secondary	Antibody Concentrations Against Vaccine Pneumococcal Serotypes	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.	At 6 years of age
Secondary	Concentration of Antibodies Against Protein D	Concentrations were expressed as GMCs in enzyme-linked immunosorbent-assay (ELISA) units per milliliter (EL.U/mL).	At 6 years of age
Secondary	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values as Measured by ELISA.	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.	At 3 and 4 years of age
Secondary	Anti-HBs Antibody Concentrations as Measured by ELISA	Concentrations were expressed as GMCs in mIU/mL.	At 3 and 4 years of age
Secondary	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above Cut-off Values	Cut-off values assessed were defined as equal to or above (=) 6.2 milli-international units per milliliter (mIU/mL), 10 mIU/mL and 100 mIU/mL.; Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL) when tested by Enzyme-Linked Immunosorbent Assay (ELISA). The tables show both the results obtained by ELISA as well as updated results following complete retesting and reanalysis by a Chemiluminescence immunoassay (CLIA). Anti-HBs seroprotection was redefined as CLIA concentration above 10 mIU/mL.	At 3, 4 and 6 years of age
Secondary	Anti-HBs Antibody Concentrations	Concentrations were expressed as GMCs in mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL) when tested by ELISA. The tables show both the results obtained by ELISA as well as updated results following complete retesting and reanalysis by a Chemiluminescence immunoassay (CLIA).	At 3, 4 and 6 years of age
Secondary	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, 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.	From last study contact of the study (NCT00463437) at 17-24 months of age until 6 years of age

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