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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Haemophilus Influenzae Type b, Neisseria Meningitidis

Intervention / Treatment
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* Biological: Haemophilus influenzae type b and meningococcal serogroup C (vaccine)
* Biological: Priorix™
* Biological: Hiberix™
* Biological: Meningitec™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 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 |
| --- | --- |
| Active Comparator: Meningitec + Hiberix Group<br>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™<br>* One subcutaneous dose at 12-18 months of age<br>Biological: Hiberix™<br>* One intramuscular dose at 12-18 months of age.<br>Biological: Meningitec™<br>* One intramuscular dose at 12-18 months of age<br>|
| Experimental: Menitorix Group<br>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)<br>* One intramuscular dose at 12-18 months of age<br>* Other names: Menitorix™;Biological: Priorix™<br>* One subcutaneous dose at 12-18 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 Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL) | Anti-PRP antibody concentration greater than or equal to 0.15 µg/mL is indicative of short-term protection. | 1 month after vaccination | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Greater Than or Equal to 1:8 Titer | rSBA-MenC titers greater than or equal to 1:8 titer are indicative of seroprotection. | 1 month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values | 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. | Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values | 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. | 5 years after vaccination | 
| Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers | 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. | Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination. | 
| Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers | 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 years after vaccination | 
| Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values | 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). | Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination | 
| Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values | 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). | 5 years after vaccination | 
| Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations | Concentrations are given as Geometric Mean Concentrations (GMCs). | Prior to, 1 month , 1 year, 2 years, 3 years and 4 years after vaccination | 
| Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations | Concentrations are given as Geometric Mean Concentrations (GMCs). | 5 years after vaccination | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Above the Cut-off Values | Anti-PSC antibody concentration cut-off values assessed include greater than or equal to (≥) 0.30 µg/mL and ≥ 2.0 µg/mL. | Prior to, 1 month, 1 year, 2 years and 3 years after vaccination | 
| Anti-polysaccharide C (Anti-PSC) Antibody Concentrations | Concentrations given as Geometric Mean Concentrations (GMCs). | Prior to, 1 month, 1 year, 2 years and 3 years after vaccination | 
| Number of Subjects Reporting Solicited Local and General Symptoms | 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. | Within 4 days (Day 0 -Day 3) after vaccination | 
| Number of Subjects Reporting Unsolicited Symptoms | 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. | Within 31 days (Day 0 - Day 30) after vaccination | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | 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. | Throughout the entire study period (up to year 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal serogroup C diseases, H.influenzae type b diseases