Study of Long-term Antibody Persistence After a Booster Dose of Menitorix Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00454987
First received: March 30, 2007
Last updated: November 12, 2015
Last verified: October 2015

March 30, 2007
November 12, 2015
May 2007
May 2010   (final data collection date for primary outcome measure)
  • Number of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above 1:8 [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:8, resulting in 50% inhibition.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:128, resulting in 50% inhibition.
  • rSBA-MenC Antibody Titers [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    Antibody concentrations for the serogroup C serum bactericidal assay using baby rabbit complement were expressed as geometric mean titers (GMT) with 95% confidence intervals (CI). Titers bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥1:8 [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:8, resulting in 50% inhibition.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8 [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:8, resulting in 50% inhibition.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:128, resulting in 50% inhibition.
  • rSBA-MenC Antibody Titers [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-serogroup C serum bactericidal assay using baby rabbit complement were expressed as geometric mean titers (GMT) with 95% confidence intervals (CI). Titers bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8 [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:8, resulting in 50% inhibition.
  • Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    The anti-meningococcal serogroup C activity was determined using a serum bactericidal test. The cut-off of the assay is a dilution of 1:128, resulting in 50% inhibition.
  • rSBA-MenC Antibody Titers [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-serogroup C serum bactericidal assay using baby rabbit complement were expressed as geometric mean titers (GMT) with 95% confidence intervals (CI). Titers bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
  • Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibodies Equal to or Above 0.15 Micrograms Per Milliliter (µg/mL) and Equal to or Above 1 Micrograms Per Milliliter (µg/mL) [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PRP Antibodies [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Number of Subjects With Anti-PRP Antibodies ≥0.15 µg/mL and ≥1 µg/mL [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PRP Antibodies [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PRP Antibodies [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-serogroup C Polysaccharide (Anti-PSC) Antibody Concentrations Equal to or Above 0.3 Micrograms Per Milliliter(µg/mL) and Equal to or Above 2 Micrograms Per Milliliter (µg/mL) [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PSC Antibodies [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polysaccharide C were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PSC Antibodies [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polysaccharide C were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PSC Antibodies [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-polysaccharide C were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations bellow the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
  • Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations Equal to or Above 5.0 ELISA Units Per Milliliter (EL.U/mL) [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    The anti-pertussis toxoid, anti-filamentous haemagglutin, anti-pertactin activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-pertussis toxoid, anti-filamentous haemagglutin and anti-pertactin C were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in EL.U/mL.
  • Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations ≥ 5.0 EL.U/mL [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    The anti-pertussis toxoid, anti-filamentous haemagglutin, anti-pertactin activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
  • Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: At Year 4 ] [ Designated as safety issue: No ]
    Antibody concentrations for anti-pertussis toxoid, anti-filamentous haemagglutin and anti-pertactin were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in EL.U/mL.
  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Up to Month 12 (Booster vaccination) ] [ Designated as safety issue: No ]
    A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.
  • Number of Subjects With SAE(s) [ Time Frame: Up to Month 24 (Booster vaccination) ] [ Designated as safety issue: No ]
    A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.
  • Number of Subjects With SAE(s) [ Time Frame: Up to Month 48 (Booster vaccination) ] [ Designated as safety issue: No ]
    A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.
  • Number of Subjects With SAE(s) [ Time Frame: Within (31-Days) at Year 2 ] [ Designated as safety issue: No ]
    A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination.
In all subjects at 12, 24 & 48 months after booster: Immunogenicity to vaccine antigens
Complete list of historical versions of study NCT00454987 on ClinicalTrials.gov Archive Site
Not Provided
Related SAEs from last study contact of booster study to end of this persistence study.
Not Provided
Not Provided
 
Study of Long-term Antibody Persistence After a Booster Dose of Menitorix Vaccine
Assessment of Long-term Antibody Persistence After a Booster Dose of GSK Biologicals' Hib & Meningococcal C Vaccine (Menitorix™) 811936 Given at 12-15 Months of Age to Subjects Primed With 3 Doses of Menitorix™ at 2, 3, 4 Months of Age

The purpose of this study is to evaluate the long-term antibody persistence at 12, 24 and 48 months after the administration of a booster dose of Menitorix™, given at 12-15 months of age. The children had previously received 3 doses of Menitorix™ and Infanrix™ IPV or Meningitec™ and Pediacel™ in infancy. In addition, the antibody persistence is to be investigated in children of 40-43 months of age who received a 3-dose primary vaccination of a MenC conjugate vaccine and a Hib containing vaccine in infancy without a booster dose of MenC conjugate and Hib vaccine in the second year of life.

This protocol posting deals with objectives & outcome measures of the extension phases at 12, 24 and 48 months after the booster phase. The objectives & outcome measures of the primary phase & booster phase at 12 to 15 months are presented in a separate protocol posting (NCT number =00258700 ).

This multicentre & multicountry study is open and has 2 study groups at Visits 1 and 3 (HibMenC and LicMenC). An additional control group in the UK at the time of the second year follow-up for persistence (subjects aged 40-43 months primed with MenC conjugate and Hib vaccines in infancy with no subsequent booster dose, group NoBoost at Visit 2). These subjects will receive a Hib catch-up vaccine at 40-43 months of age. The subjects of groups HibMenC and LicMenC were randomized in the primary vaccination study 103974 and will not be further randomized. The subjects of group NoBoost will not be randomized. All subjects at the UK centre will receive Infanrix™-IPV at the second visit (i.e. 24 months after Menitorix™ booster or at 40-43 months of age). In addition, the subjects of group NoBoost will receive a Hib catch-up vaccine (Menitorix™) at the same visit.

Subjects of groups HibMenC and LicMenC will have 3 blood samples taken for immunogenicity analyses: at 12, 24 & 48 months after the booster vaccination. Subjects of group NoBoost will have 1 blood sample taken for immunogenicity analyses at 40-43 months of age. 75 new subjects will be enrolled in this study (group NoBoost).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Haemophilus Influenzae Type b
  • Neisseria Meningitidis
  • Biological: Menitorix
    Menitorix was only administered to subjects of the group NoBoost at 40 to 43 months of age.
  • Biological: Infanrix IPV
    Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.
  • Experimental: Group HibMenC
    Previously primed in infancy with Hib-MenC and Infanrix-IPV and boosted with Hib-MenC (Priorix co-administered). All UK subjects received a booster dose of Infanrix IPV at 40 to 43 months of age. 3 doses of Meningitec: 2 administered by intramuscular injection (IM) in the right thigh and one in the deltoid; and one dose of Infnrix-IPV administered by IM in the left thigh.
    Intervention: Biological: Infanrix IPV
  • Active Comparator: Group LicMenC
    Previously primed in infancy with Meningitec and Pediacel and boosted with Hib-MenC (Priorix co-administered). All UK subjects received a booster dose of Infanrix IPV at 40 to 43 months of age. 2 doses of Meningitec: one administered by IM injection in the right thigh and one in the deltoid; one dose of Pediacel administered by IM injection in the letf thigh; and one dose of Priorix administered subcutaneous in the left arm.
    Intervention: Biological: Infanrix IPV
  • Active Comparator: Group NoBoost
    Previously primed (according to the routine UK immunisation schedule) with 3 doses of a MenC conjugate vaccine and a Hib containing vaccine before the age of 8 months without booster dose at 12 months of age (only for UK). All subjects received a booster dose of Infanrix IPV and Menitorix at 40 to 43 months of age. One dose of Infnrix-IPV administered by IM injection in the left thigh and one dose of Menitorix.
    Interventions:
    • Biological: Menitorix
    • Biological: Infanrix IPV

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
288
May 2010
May 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

Subjects of groups HibMenC and LicMenC at Visits 1, 2 and 3:

  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
  • A male or female between and including 24 and 31 months of age at the time of Visit 1, between and including 40 and 43 months of age at Visit 2 and between and including 60 and 64 months at 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.
  • Having completed the booster vaccination study 104056.

Subjects of group NoBoost at Visit 2 (UK only):

  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
  • A male or female between and including 40 and 43 months of age at Visit 2.
  • 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.
  • Having received a 3-dose primary vaccination with a MenC conjugate vaccine and a Hib containing vaccine before the age of 8 months.

Exclusion Criteria:

  • Previous administration of booster dose of Hib or meningococcal serogroup C except booster study vaccines during the study 104056.
  • History of H. influenzae type b or meningococcal diseases.
  • For UK subjects of groups HibMenC and LicMenC only: previous administration of a booster dose of a pertussis-containing vaccine except booster study vaccines during the study 104056.
Both
24 Months to 64 Months   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
Poland,   United Kingdom
 
NCT00454987
109664, 109666, 109668
Not Provided
Not Provided
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP