Clinical trial NCT00454987: Study of Long-term Antibody Persistence After a Booster Dose of Menitorix Vaccine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-02
Enrollment: 288
Sex: ALL
Minimum age (years): 24
Maximum age (years): 64
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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).

Eligibility 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.

Primary outcomes:
measure: Number of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above 1:8
timeFrame: At Year 1
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128
timeFrame: At Year 1
measure: rSBA-MenC Antibody Titers
timeFrame: At Year 1
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥1:8
timeFrame: At Year 2
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8 for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128
timeFrame: At Year 2
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128 for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: rSBA-MenC Antibody Titers
timeFrame: At Year 2
measure: rSBA-MenC Antibody Titers for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:8
timeFrame: At Year 4
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ 1:128
timeFrame: At Year 4
measure: rSBA-MenC Antibody Titers
timeFrame: At Year 4
measure: 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)
timeFrame: At Year 1
measure: Concentration of Anti-PRP Antibodies
timeFrame: At Year 1
measure: Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL
timeFrame: At Year 2
measure: Number of Subjects With Anti-PRP Antibodies ≥0.15 µg/mL and ≥1 µg/mL for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Concentration of Anti-PRP Antibodies
timeFrame: At Year 2
measure: Concentration of Anti-PRP Antibodies for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Number of Subjects With Anti-PRP Antibodies ≥ 0.15 µg/mL and ≥ 1 µg/mL
timeFrame: At Year 4
measure: Concentration of Anti-PRP Antibodies
timeFrame: At Year 4
measure: 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)
timeFrame: At Year 1
measure: Concentration of Anti-PSC Antibodies
timeFrame: At Year 1
measure: Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL
timeFrame: At Year 2
measure: Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Concentration of Anti-PSC Antibodies
timeFrame: At Year 2
measure: Concentration of Anti-PSC Antibodies for Meningitec+Hiberix Group
timeFrame: At Year 2
measure: Number of Subjects With Anti-PSC Antibody Concentrations ≥ 0.3 µg/mL and ≥ 2 µg/mL
timeFrame: At Year 4
measure: Concentration of Anti-PSC Antibodies
timeFrame: At Year 4
measure: 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)
timeFrame: At Year 2
measure: Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies
timeFrame: At Year 2
measure: Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations ≥ 5.0 EL.U/mL
timeFrame: At Year 4
measure: Concentration of Anti-PT, Anti-FHA and Anti-PRN Antibodies
timeFrame: At Year 4
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to Month 12 (Booster vaccination)
measure: Number of Subjects With SAE(s)
timeFrame: Up to Month 24 (Booster vaccination)
measure: Number of Subjects With SAE(s)
timeFrame: Up to Month 48 (Booster vaccination)
measure: Number of Subjects With SAE(s)
timeFrame: Within (31-Days) at Year 2
Secondary outcomes:
Other outcomes:
Locations:
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Kielce
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Leczna
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Trzebnica
country: Poland
facility: GSK Investigational Site
city: Oxford
country: United Kingdom
facility: GSK Investigational Site
state: Oxfordshire
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.