Haemophilus Influenzae Type bPhase 4NCT00454987
Study of Long-term Antibody Persistence After a Booster Dose of Menitorix Vaccine
A Phase 4 study testing Menitorix and Infanrix IPV in people with Haemophilus Influenzae Type b and Neisseria Meningitidis, run by GlaxoSmithKline at 9 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 24 to 64 monthsHealthy volunteers can take part
- Conditions the study is for
- Haemophilus Influenzae Type b, Neisseria Meningitidis, Neisseria Meningitidis-Haemophilus Influenzae Type b Vaccine
- What is being tested?
- Menitorix and Infanrix IPV
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 288 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 16 May 2007to 12 Oct 2007
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 64 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Poland8 sites
GSK Investigational Site
Bydgoszcz, 85-021
GSK Investigational Site
Gdansk, 80-394
GSK Investigational Site
Kielce, 25-711
GSK Investigational Site
Krakow, 31-202
GSK Investigational Site
Łęczna, 21-010
GSK Investigational Site
Poznan, 61-709
GSK Investigational Site
Siemianowice Śląskie, 41-103
GSK Investigational Site
Trzebnica, 55-100
United Kingdom1 site
GSK Investigational Site
Oxford, Oxfordshire, OX3 7LJ
About this study
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
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)
Read the 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).
- Conditions
- Haemophilus Influenzae Type b, Neisseria Meningitidis, Neisseria Meningitidis-Haemophilus Influenzae Type b Vaccine
- Being tested
- Menitorix, Infanrix IPV
- Keywords
- antibody persistence, Meningococcal serogroup C vaccine, conjugate vaccine, Haemophilus influenzae type b vaccine
- Medical subject headings
- Haemophilus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MenitorixBiological
Menitorix was only administered to subjects of the group Meningitic+Hiberix group at 40 to 43 months of age.
Infanrix IPVBiological
Infanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age.
| Study group | Role | What they receive |
|---|---|---|
| Menitorix Group | Experimental | 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. Receives: Biological: Infanrix IPV |
| Meningitec Group | Active comparator | 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. Receives: Biological: Infanrix IPV |
| Meningitec+Hiberix Group | Active comparator | 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. Receives: Biological: Menitorix; Biological: Infanrix IPV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Within (31-Days) at Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2007 (estimated)
- Study start16 May 2007
- Primary completion12 Oct 2007
- Study completion12 Oct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Haemophilus Influenzae Type bStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 288 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00454987
- Sponsor's protocol ID
- 109664
- Other IDs
- 109666, 109668, 2006-006460-32
- Status last verified
- Jun 2020
- First submitted
- 30 Mar 2007
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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.
PubMed 20844459Khatami 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.
PubMed 22673139Khatami 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.
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00454987
- Acronym / sponsor ID
- 109664
- Conditions
- Haemophilus Influenzae Type b, Neisseria Meningitidis, Neisseria Meningitidis-Haemophilus Influenzae Type b Vaccine
- Keywords
- antibody persistence, Meningococcal serogroup C vaccine, conjugate vaccine, Haemophilus influenzae type b vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 288 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 16 May 2007 (actual)
- Primary completion
- 12 Oct 2007 (actual)
- Study completion
- 12 Oct 2007 (actual)
- First posted
- 2 Apr 2007 (estimated)
- Results
- Posted 16 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Menitorix Group | Experimental | Biological: Infanrix IPVPreviously 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. |
| Meningitec Group | Active comparator | Biological: Infanrix IPVPreviously 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. |
| Meningitec+Hiberix Group | Active comparator | Biological: Menitorix, Biological: Infanrix IPVPreviously 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. |
Who may qualify
- Ages
- 24 to 64 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MenitorixMenitorix was only administered to subjects of the group Meningitic+Hiberix group at 40 to 43 months of age. | Biological | Meningitec+Hiberix Group |
| Infanrix IPVInfanrix IPV was administered according to the manufacturer's instructions to UK subjects at 40 to 43 months of age. | Biological | Meningitec Group, Meningitec+Hiberix Group, Menitorix Group |
Primary outcome
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
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
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
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
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 for Meningitec+Hiberix Group
Time frame: At Year 2
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
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.
Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 for Meningitec+Hiberix Group
Time frame: At Year 2
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
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.
rSBA-MenC Antibody Titers for Meningitec+Hiberix Group
Time frame: At Year 2
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
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
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
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
The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PRP Antibodies
Time frame: At Year 1
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
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 for Meningitec+Hiberix Group
Time frame: At Year 2
The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PRP Antibodies
Time frame: At Year 2
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.
Concentration of Anti-PRP Antibodies for Meningitec+Hiberix Group
Time frame: At Year 2
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.
Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL
Time frame: At Year 4
The anti-polyribosylribitol phosphate was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PRP Antibodies
Time frame: At Year 4
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.
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
The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PSC Antibodies
Time frame: At Year 1
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
The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL for Meningitec+Hiberix Group
Time frame: At Year 2
The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PSC Antibodies
Time frame: At Year 2
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.
Concentration of Anti-PSC Antibodies for Meningitec+Hiberix Group
Time frame: At Year 2
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
The anti-polysaccharide C activity was determined using an Enzyme-linked Immunosorbent Assay (ELISA).
Concentration of Anti-PSC Antibodies
Time frame: At Year 4
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
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
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
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
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)
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)
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)
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
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20844459Khatami 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.
- Background: PubMed 22673139Khatami 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.
- BackgroundKhatami 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.
- BackgroundKhatami 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.
- BackgroundSnape 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Menitorix and Infanrix IPV in people with Haemophilus Influenzae Type b and Neisseria Meningitidis, run by GlaxoSmithKline at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 36 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00454987, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.