Study in Toddlers to Demonstrate Non-inferiority of GSK Biologicals' Hib-MenC & to Evaluate Persistence up to 5 Years.

Study Description

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Brief Summary:

The purpose of the primary phase of the study is to demonstrate the non-inferiority of a single dose of GSK Biologicals' Haemophilus influenzae type b and meningococcal C (Hib-MenC) conjugate vaccine when given in the second year of life to subjects primed in infancy with a Hib vaccine, but not with a meningococcal serogroup C vaccine, versus commercially available Hib and MenC vaccines.

In the extension phase, at Years 1, 2, 3, 4 & 5, one blood sample is taken at each year to follow the antibody persistence up to 5 years after vaccination. No additional vaccine is administered during the extension phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or disease	Intervention/treatment	Phase
Haemophilus Influenzae Type b; Neisseria Meningitidis	Biological: Haemophilus influenzae type b and meningococcal serogroup C (vaccine); Biological: Priorix™; Biological: Hiberix™; Biological: Meningitec™	Phase 3

Detailed Description:

This multicenter study is open and has 2 treatment groups with Hiberix™ + a commercially available MenC vaccine as active controls. Priorix™ is given concomitantly in both groups. In the primary phase, two blood samples are taken from all subjects for immunogenicity analyses: before and one month after vaccination. In the extension phase, at Year 1, 2, 3, 4 & 5, one blood sample is taken at each year to follow the antibody persistence up to 5 years after vaccination. No additional vaccine is administered during the extension phase.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	433 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Study to Demonstrate Non-inferiority of GSK Biologicals' Hib-MenC With Priorix™, Versus MenC-CRM197 Vaccine With Hiberix™ & Priorix™ in Toddlers Primed With Hib But Not MenC & to Evaluate Persistence up to 5 Years After Vaccination.
Study Start Date :	June 1, 2006
Actual Primary Completion Date :	November 1, 2007
Actual Study Completion Date :	November 6, 2007

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Meningitec + Hiberix Group; Subjects received a single dose of Meningitec™ vaccine co-administered with Hiberix™ and Priorix™ vaccines. The Meningitec vaccine was administered intramuscularly in the left deltoid region, the Hiberix vaccine was administered intramuscularly in the left thigh region and the Priorix vaccine was administered subcutaneously in the right upper arm.	Biological: Priorix™; One subcutaneous dose at 12-18 months of age; Biological: Hiberix™; One intramuscular dose at 12-18 months of age.; Biological: Meningitec™; One intramuscular dose at 12-18 months of age
Experimental: Menitorix Group; Subjects received a single dose of Menitorix™ vaccine co-administered with Priorix™ vaccine. Menitorix vaccine was administered intramuscularly in the left deltoid region and the Priorix vaccine was administered subcutaneously in the right upper arm.	Biological: Haemophilus influenzae type b and meningococcal serogroup C (vaccine); One intramuscular dose at 12-18 months of age; Other Names: Hib-MenC; Menitorix™; Biological: Priorix™; One subcutaneous dose at 12-18 months of age

Outcome Measures

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Primary Outcome Measures :

1. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL) [ Time Frame: 1 month after vaccination ]
   Anti-PRP antibody concentration greater than or equal to 0.15 µg/mL is indicative of short-term protection.
2. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Greater Than or Equal to 1:8 Titer [ Time Frame: 1 month after vaccination ]
   rSBA-MenC titers greater than or equal to 1:8 titer are indicative of seroprotection.

Secondary Outcome Measures :

1. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values [ Time Frame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination ]

   rSBA-MenC titers cut-off values assessed were greater than or equal to (≥) 1:8 (indicative of seroprotection) and ≥ 1:128 titers.

   Functional anti-meningococcal serogroup C activity (SBA-MenC) was determined by a serum bactericidal test using rabbit complement. For SBA testing at a GlaxoSmithKline (GSK) laboratory up to Year 3 after vaccination, titres were expressed as the reciprocal of the dilution resulting in 50% inhibition. For SBA testing at the Public Health England (PHE), formerly known as Health Protection Agency (HPA), at Year 4, titres were expressed as the reciprocal of the last dilution resulting in at least 50% inhibition.

2. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values [ Time Frame: 5 years after vaccination ]
   rSBA-MenC titers cut-off values assessed were greater than or equal to (≥)1:8 (indicative of seroprotection) and 1:128 titers. For SBA testing at the PHE at Year 5, titres were expressed as the reciprocal of the last dilution resulting in at least 50% inhibition.
3. Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers [ Time Frame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination. ]
   Titers are given as Geometric Mean Titers (GMTs). Functional anti-meningococcal serogroup C activity (SBA-MenC) was determined by a serum bactericidal test using rabbit complement. For SBA testing at a GlaxoSmithKline (GSK) laboratory up to Year 3 after vaccination, titres were expressed as the reciprocal of the dilution resulting in 50% inhibition. For SBA testing at the PHE at year 4 after vaccination, titres were expressed as the reciprocal of the last dilution resulting in at least 50% inhibition.
4. Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers [ Time Frame: 5 years after vaccination ]
   Titers are given as Geometric Mean Titers (GMTs). Functional anti-meningococcal serogroup C activity (SBA-MenC) was determined by a serum bactericidal test using rabbit complement. For SBA testing at the PHE at Year 5, titres were expressed as the reciprocal of the last dilution resulting in at least 50% inhibition.
5. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values [ Time Frame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination ]
   Anti-PRP antibody concentration cut-off values assessed include 0.15 µg/mL (indicative of short-term protection) and 1.0 µg/mL (indicative of long-term protection).
6. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values [ Time Frame: 5 years after vaccination ]
   Anti-PRP antibody concentration cut-off values assessed include 0.15 µg/mL (indicative of short-term protection) and 1.0 µg/mL (indicative of long-term protection).
7. Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations [ Time Frame: Prior to, 1 month , 1 year, 2 years, 3 years and 4 years after vaccination ]
   Concentrations are given as Geometric Mean Concentrations (GMCs).
8. Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations [ Time Frame: 5 years after vaccination ]
   Concentrations are given as Geometric Mean Concentrations (GMCs).
9. Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Above the Cut-off Values [ Time Frame: Prior to, 1 month, 1 year, 2 years and 3 years after vaccination ]
   Anti-PSC antibody concentration cut-off values assessed include greater than or equal to (≥) 0.30 µg/mL and ≥ 2.0 µg/mL.
10. Anti-polysaccharide C (Anti-PSC) Antibody Concentrations [ Time Frame: Prior to, 1 month, 1 year, 2 years and 3 years after vaccination ]
    Concentrations given as Geometric Mean Concentrations (GMCs).
11. Number of Subjects Reporting Solicited Local and General Symptoms [ Time Frame: Within 4 days (Day 0 -Day 3) after vaccination ]

    Solicited local symptoms assessed include pain, redness and swelling at the injection site.

    Solicited general symptoms assessed include drowsiness, fever (≥ 38°C), irritability and loss of appetite.

12. Number of Subjects Reporting Unsolicited Symptoms [ Time Frame: Within 31 days (Day 0 - Day 30) after vaccination ]
    Unsolicited symptom: Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
13. Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period (up to year 5) ]

    A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject.

    For the long-term persistence phase (Years 1 through 5), only those SAEs that are determined by the investigator to have a causal relationship to the vaccination will be described individually.

Eligibility Criteria

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Ages Eligible for Study:	12 Months to 18 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Primary phase:

• Subjects whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including, 12 and 18 months of age at the time of vaccination.
• Written informed consent obtained from the parent or guardian of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Previously completed routine childhood vaccinations to the best of his/her parents'/guardians knowledge.
• Having completed primary vaccination with two doses of Haemophilus influenzae type b outer membrane protein (Hib-OMP) containing vaccine OR three doses of diphtheria, tetanus, acellular pertussis and Haemophilus influenzae type b (DTPa/Hib) containing vaccine at least 6 months before the study start.

Long-term persistence phase:

- Having participated in the vaccination study 106445

Exclusion Criteria:

For the primary vaccination phase:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) or planned administration of immuno-suppressants or other immune-modifying drugs within six months prior to vaccination.
• Planned administration/administration of a vaccine not foreseen by the protocol during the period starting from 30 days before vaccination and ending 30 days after vaccination.
• Administration of a meningococcal vaccine not foreseen by the study protocol during the period starting at birth and ending at first dose.
• Previous administration of a booster dose of Hib vaccine.
• Previous vaccination against measles, mumps, rubella.
• History of H. influenzae type b, meningococcal serogroup C and/or confirmed measles, mumps or rubella diseases.
• Known exposure to measles, mumps or rubella within 30 days prior to the start of the study.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of neurological disorders or more than one episode of febrile convulsion.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Additional exclusion criteria for the long-term persistence phase: to be checked each year.

• Previous administration of a booster dose of Hib, meningococcal serogroup C vaccines.
• History of H. influenzae type b, meningococcal serogroup C diseases.

Contacts and Locations

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Locations

Australia, Australian Capital Territory
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Australia, Queensland
GSK Investigational Site
Herston, Queensland, Australia, 4029
Australia, South Australia
GSK Investigational Site
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
GSK Investigational Site
Carlton, Victoria, Australia, 3053
Australia, Western Australia
GSK Investigational Site
Perth, Western Australia, Australia

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

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 Data/Documents: Statistical Analysis Plan 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 106445
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

Booy R, Richmond P, Nolan T, McVernon J, Marshall H, Nissen M, Reynolds G, Ziegler JB, Heron L, Lambert S, Caubet M, Mesaros N, Boutriau D. Immediate and longer term immunogenicity of a single dose of the combined haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in primed toddlers 12 to 18 months of age. Pediatr Infect Dis J. 2011 Apr;30(4):340-2. doi: 10.1097/INF.0b013e31820013d2.

Booy R, Richmond P, Nolan T, McVernon J, Marshall H, Nissen M, Reynolds G, Ziegler JB, Stoney T, Heron L, Lambert S, Mesaros N, Peddiraju K, Miller JM. Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers. Pediatr Infect Dis J. 2013 Feb;32(2):169-74. doi: 10.1097/INF.0b013e3182787bff.

Booy R et al. Immunogenicity and safety of the Hib-MenC-TT conjugate vaccine in Hib-primed toddlers: 3 year follow-up. Abstract presented at the 7th World Congress for World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011.

Booy R et al. Immunogenicity and safety of the Hib-MenC-TT conjugate vaccine in Hib-primed toddlers: 4 year follow-up. Abstract presented at the Communicable Diseases Network Australia - Communicable Diseases Control Conference 2013, Canberra, Australia, 19-20 March 2013.

Booy R et al. Prolonged immunogenicity and safety of the HibMenC-TT conjugate vaccine in Hib-Primed toddlers. Abstract presented at the PHAA Communicable Disease Conference. Canberra, Australia, 4-6 April 2011.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00326118 History of Changes
Other Study ID Numbers:	106445; 106446 ( Other Identifier: GSK ); 106449 ( Other Identifier: GSK ); 106450 ( Other Identifier: GSK ); 106452 ( Other Identifier: GSK ); 106454 ( Other Identifier: GSK )
First Posted:	May 16, 2006
Results First Posted:	October 23, 2009
Last Update Posted:	August 24, 2018
Last Verified:	September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
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.

Keywords provided by GlaxoSmithKline:

Meningococcal serogroup C diseases; H.influenzae type b diseases

Additional relevant MeSH terms:

Vaccines; Immunologic Factors; Physiological Effects of Drugs