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
  Purpose

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 ).


Condition Intervention Phase
Haemophilus Influenzae Type b
Neisseria Meningitidis
Biological: Menitorix
Biological: Infanrix IPV
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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.


Enrollment: 288
Study Start Date: May 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Infanrix IPV
Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.
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.
Biological: Infanrix IPV
Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.
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.
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.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   24 Months to 64 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00454987

Locations
Poland
GSK Investigational Site
Bydgoszcz, Poland, 85-021
GSK Investigational Site
Gdansk, Poland, 80-394
GSK Investigational Site
Kielce, Poland, 25-711
GSK Investigational Site
Krakow, Poland, 31-202
GSK Investigational Site
Leczna, Poland, 21-010
GSK Investigational Site
Poznan, Poland, 61-709
GSK Investigational Site
Siemianowice Slaskie, Poland, 41-103
GSK Investigational Site
Trzebnica, Poland, 55-100
United Kingdom
GSK Investigational Site
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Khatami A et al. Persistence of antibody response following a booster dose of Hib-MenC-TT glycoconjugate vaccine: A phase IV open randomized controlled trial. Abstract presented at the 27th annual ESPID meeting, Brussels, Belgium, 9-13 June 2009.
Khatami A et al. Antibody concentrations against pertussis antigens at age 5 years following infant and pre-school immunisation: follow-on of a randomized controlled trial. Abstract presented at the 7th World Congress for World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011.
Snape MD et al. Persistence of antibody response following a booster dose of Hib-MenC-TT glycoconjugate vaccine to five years: a follow-on study. Abstract presented at the 7th World Congress for World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011.

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00454987     History of Changes
Other Study ID Numbers: 109664  109666  109668 
Study First Received: March 30, 2007
Results First Received: November 12, 2015
Last Updated: November 12, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
antibody persistence
Meningococcal serogroup C vaccine
conjugate vaccine
Haemophilus influenzae type b vaccine

ClinicalTrials.gov processed this record on February 10, 2016