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 links to objectives and outcome measures of the primary phase & booster phase at 12 to 15 months are provided below:

https://www.gsk-studyregister.com/study/2747 (Primary phase) https://www.gsk-studyregister.com/study/2755 (Booster phase)

Study Overview

• Status: Completed
• Conditions: Neisseria Meningitidis; Haemophilus Influenzae Type b; Neisseria Meningitidis-Haemophilus Influenzae Type b Vaccine
• Intervention / Treatment: Biological: Infanrix IPV; Biological: Menitorix

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).

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • 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
    • GSK Investigational Site
• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menitorix Group; Previously primed in infancy with Menitorix™ and Infanrix-IPV™ and boosted with Menitorix™ (Priorix™ co-administered). All UK subjects received a booster dose of Infanrix-IPV™ at 40 to 43 months of age, intramuscularly in the deltoid region.	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: Meningitec Group; Previously primed in infancy with Meningitec™ and Pediacel™ and boosted with Menitorix™ (Priorix™ co-administered). All UK subjects received a booster dose of Infanrix-IPV™ at 40 to 43 months of age, intramuscularly in the deltoid region.	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: Meningitec+Hiberix Group; Previously primed (according to the routine UK immunisation schedule) with 3 doses of a Meningitec™ conjugate vaccine and a Hiberix™ 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, intramuscularly in the deltoid region. This group was added only at year 2 in UK (Meningitec+Hiberix Group) to comply with UK Hib Catch-up vaccination programme.	Biological: Infanrix IPV; Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.; Biological: Menitorix; Menitorix was only administered to subjects of the group Meningitic+Hiberix group at 40 to 43 months of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above 1:8	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.	At Year 1
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128	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.	At Year 1
rSBA-MenC Antibody Titers	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.	At Year 1
Number of Subjects With rSBA-MenC Antibody Titers ≥1:8	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.	At Year 2
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8 for Meningitec+Hiberix Group	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.	At Year 2
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128	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.	At Year 2
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 for Meningitec+Hiberix Group	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.	At Year 2
rSBA-MenC Antibody Titers	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 below the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	At Year 2
rSBA-MenC Antibody Titers for Meningitec+Hiberix Group	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.	At Year 2
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8	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.	At Year 4
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128	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.	At Year 4
rSBA-MenC Antibody Titers	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.	At Year 4
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)	The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 1
Concentration of Anti-PRP Antibodies	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.	At Year 1
Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL	The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 2
Number of Subjects With Anti-PRP Antibodies ≥0.15 µg/mL and ≥1 µg/mL for Meningitec+Hiberix Group	The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 2
Concentration of Anti-PRP Antibodies	Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations below the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	At Year 2
Concentration of Anti-PRP Antibodies for Meningitec+Hiberix Group	Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations below the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	At Year 2
Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL	The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 4
Concentration of Anti-PRP Antibodies	Antibody concentrations for anti-polyribosylribitol phosphate were expressed as geometric mean concentrations (GMC) with 95% confidence intervals (CI), given in µg/mL. Concentrations below the cut-off of the test were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	At Year 4
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)	The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 1
Concentration of Anti-PSC Antibodies	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.	At Year 1
Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL	The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 2
Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL for Meningitec+Hiberix Group	The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 2
Concentration of Anti-PSC Antibodies	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.	At Year 2
Concentration of Anti-PSC Antibodies for Meningitec+Hiberix Group	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.	At Year 2
Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL	The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 4
Concentration of Anti-PSC Antibodies	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.	At Year 4
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)	The anti-pertussis toxoid, anti-filamentous haemagglutin, anti-pertactin activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 2
Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies	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.	At Year 2
Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations ≥ 5.0 EL.U/mL	The anti-pertussis toxoid, anti-filamentous haemagglutin, anti-pertactin activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).	At Year 4
Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies	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.	At Year 4
Number of Subjects With Serious Adverse Events (SAEs)	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.	Up to Month 12 (Booster vaccination)
Number of Subjects With SAE(s)	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.	Up to Month 24 (Booster vaccination)
Number of Subjects With SAE(s)	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.	Up to Month 48 (Booster vaccination)
Number of Subjects With SAE(s)	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.	Within (31-Days) at Year 2

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Khatami A, Snape MD, John T, Westcar S, Klinger C, Rollinson L, Boutriau D, Mesaros N, Wysocki J, Galaj A, Yu LM, Pollard AJ. Persistence of immunity following a booster dose of Haemophilus influenzae type B-Meningococcal serogroup C glycoconjugate vaccine: follow-up of a randomized controlled trial. Pediatr Infect Dis J. 2011 Mar;30(3):197-202. doi: 10.1097/INF.0b013e3181f728fd.
• Khatami A, Snape MD, Wysocki J, John TM, Westcar S, Mesaros N, Peddiraju K, Boutriau D, Yu LM, Pollard AJ. Persistence of antibody response following a booster dose of Hib-MenC-TT glycoconjugate vaccine to five years: a follow-up study. Pediatr Infect Dis J. 2012 Oct;31(10):1069-73. doi: 10.1097/INF.0b013e318262528c.
• 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.
• 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.
• 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.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2007
• Primary Completion (Actual): October 12, 2007
• Study Completion (Actual): October 12, 2007

Study Registration Dates

• First Submitted: March 30, 2007
• First Submitted That Met QC Criteria: March 30, 2007
• First Posted (Estimate): April 2, 2007

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: conjugate vaccine; Meningococcal serogroup C vaccine; antibody persistence; Haemophilus influenzae type b vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Orthomyxoviridae Infections; Pasteurellaceae Infections; Influenza, Human; Haemophilus Infections
• Other Study ID Numbers: 109664; 109666 (Other Identifier: GSK); 109668 (Other Identifier: GSK); 2006-006460-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 109664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 109664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 109664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 109664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 109664
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register