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

Study Overview
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Brief Summary
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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)

Detailed Description
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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).

Official Title
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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

Conditions
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Haemophilus Influenzae Type b, Neisseria Meningitidis, Neisseria Meningitidis-Haemophilus Influenzae Type b Vaccine

Intervention / Treatment
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* Biological: Menitorix
* Biological: Infanrix IPV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 64 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menitorix Group<br>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<br>* Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.<br>|
| Active Comparator: Meningitec Group<br>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<br>* Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.<br>|
| Active Comparator: Meningitec+Hiberix Group<br>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: Menitorix<br>* Menitorix was only administered to subjects of the group Meningitic+Hiberix group at 40 to 43 months of age.<br>Biological: Infanrix IPV<br>* Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody persistence, Meningococcal serogroup C vaccine, conjugate vaccine, Haemophilus influenzae type b vaccine