Immune Response & Safety of GSK Biologicals' Mencevax™ ACWY in Subjects Primed in the DTPW-HBV=HIB-MENAC-TT-011 Study

Study Overview
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Brief Summary
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This study will be conducted in three stages. In the DTP booster stage at 15 to 24 months of age, all subjects will receive a booster dose of Tritanrix™-HepB/Hiberix™. In the Mencevax™ ACWY full dose stage at 24 to 30 months of age all subjects will receive a dose of Mencevax™ ACWY. In the Mencevax™ ACWY small dose stage at 30 to 36 months of age, the first 75 subjects in each of the two centers will be tested for boostability of the MenA and MenC immune response by giving a fifth of a dose of a Mencevax™ ACWY vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Subjects in the group that was previously primed with Tritanrix™-HepB/Hiberix™ will be the control group for the group that was previously primed with Tritanrix™-HepB/Hib-MenAC. Blood samples will be drawn from subjects as follows: prior to and one month after the full dose of the Mencevax™ ACWY vaccine. prior to and one month after 1/5th of a dose of Mencevax™ ACWY vaccine (only for the first 75 subjects in each of the two centers).

Official Title
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Booster Vaccination Study to Assess Immunogenicity & Safety of a Dose of GSK Biologicals' Mencevax™ ACWY & 1/5th of a Dose of Mencevax™ ACWY in Subjects Primed in the DTPW-HBV=HIB-MENAC-TT-011 Study

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Tritanrix™- HepB
* Biological: Hiberix™
* Biological: Mencevax™ ACWY


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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, 15 and 24 months of age at the time of vaccination. 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 participated in the primary vaccination study DTPW-HBV=HIB-MENAC-TT-011 (eTrack No. 100478) in Center No. 4328 or Center No.4329. Exclusion criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the vaccination, or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of vaccination; with the exception of oral poliovirus vaccine (OPV). Booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib) and/or meningococcal serogroups A and/or C disease, after the date of the study conclusion visit of the primary vaccination study DTPW-HBV=HIB-MENAC-TT-011 (eTrack No. 100478). History of diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A or C disease. Known exposure to diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A or C disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. 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 any neurologic disorders or seizures including febrile seizures in infancy. Acute disease at the time of enrolment. Planned or actual administration of immunoglobulins and/or any blood products within the three months preceding Mencevax™ ACWY vaccination.

Ages Eligible for Study
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Minimum Age: 15 Months
Maximum Age: 24 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: TRITANRIX™-HEPB/HIB-MENAC +MENCEVAX™ ACWY GROUP<br>Subjects previously primed with 3 doses of Tritanrix™-HepB/Hib-MenAC vaccine in study NCT00290303, were administered in the current study one booster dose of Tritanrix™-HepB/Hiberix™, intramuscularly in the left anterolateral thigh, at 15-24 months of age and one booster dose of Mencevax™ ACWY by subcutaneous injection in the upper region of the left arm, at 24-30 months of age. | Biological: Tritanrix™- HepB<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 24 months<br>Biological: Hiberix™<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 24 months<br>Biological: Mencevax™ ACWY<br>* One full subcutaneous dose in subjects aged 24 to 30 months or 1/5th of a dose intramuscular in subjects aged 30 to 36 months<br>|
| Active Comparator: TRITANRIX™-HEPB/HIBERIX™+MENCEVAX™ ACWY GROUP<br>Subjects previously primed with 3 doses Tritanrix™-HepB/Hiberix™ vaccine in study NCT00290303, were administered in the current study one booster dose of Tritanrix™-HepB/Hiberix™, intramuscularly in the left anterolateral thigh, at 15-24 months of age and one dose of Mencevax™ ACWY by subcutaneous injection in the upper region of the left arm, at 24-30 months of age. | Biological: Tritanrix™- HepB<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 24 months<br>Biological: Hiberix™<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 24 months<br>Biological: Mencevax™ ACWY<br>* One full subcutaneous dose in subjects aged 24 to 30 months or 1/5th of a dose intramuscular in subjects aged 30 to 36 months<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 Activity Against Neisseria Meningitidis Serogroups A, C (rSBA-MenA, C) Using Rabbit Complement Antibodies | Antibody cut-offs were higher than or equal to (≥) 1:128 | 1 month after Mencevax ACWY vaccination (at 25 to 31 months of age). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-rSBA-MenA, C Antibody Titers ≥ Pre-defined Cut-off Values | Pre-defined cut-offs were ≥ 1:8 and ≥ 1:128 | Prior to (at 24 to 30 months of age) and after (at 25 to 31 months of age) Mencevax ACWY vaccination. | 
| Anti-rSBA-MenA, C Antibody Titers | Antibody titers were expressed as Geometric Mean Titers (GMTs) | Prior to (at 24 to 30 months of age) and after (at 25 to 31 months of age) Mencevax ACWY vaccination. | 
| Number of Subjects With Anti-pilysaccharide A and C (Anti-PSA/PSC) Antibody Concentrations ≥ Predefined Cut-off Values | Antibody cut-offs were ≥ 0.3, 2 micrograms per millilitre (µg/mL). | Prior to (at 24 to 30 months of age) and after (at 25 to 31 months of age) Mencevax ACWY vaccination. | 
| Anti-PSA, Anti-PSC Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). | Prior to (at 24 to 30 months of age) and after (at 25 to 31 months of age) Mencevax ACWY vaccination. | 
| Number of Subjects With Anti-hepatitis B Surface (Anti-HBs) Antigen Antibody Concentrations ≥ Cut-offs | The antibody concentrations cut-off was ≥ 10 milli international units per millilitre (mIU/mL). | Prior to the Mencevax ACWY vaccination at 24-30 Months of age | 
| Anti-HBs Concentrations | Antibody concnetrations were expressed as Geometric Mean Concentrations (GMCs). | Prior to the Mencevax ACWY vaccination at 24-30 Months of age | 
| Number of Subjects With Vaccine Response for rSBA-Men A, C | Vaccine response was defined as follows: for initially seronegative subjects (i.e. with rSBA titer < 1:8 pre-vaccination), rSBA titer ≥ 1:32 post-vaccination (seroconversion), and for initially seropositive subjects (i.e. with rSBA > 1:8 prevaccination), at least a 4-fold increase in rSBA titer from pre-vaccination to post-vaccination. | 1 month after Mencevax ACWY vaccination (at 25 to 31 months of age). | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness, swelling. Any = symptom occurring regardless of intensity grade. | During the 4-day follow-up period after the Mencevax ACWY vaccination, at 24-30 months of age | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite, rectal fever [≥ 38 degrees Celsius (°C)]. Any = occurrence of symptom regardless of intensity grade. | During the 4-day follow-up period after the Mencevax ACWY vaccination, at 24-30 months of age | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regard-less of intensity grade or relation to vaccination. | From Day 0 at months 15-24 of age to study end at Months 25-31 of age | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From 15-24 Months of age up to Months 25-31 of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis B, meningococcal vaccine, pertussis, Prophylaxis diphtheria, meningococcal serogroups A and C diseases, tetanus, Haemophilus influenzae type b