Study to Asses DTPw-HBV/Hib at 15-18 Months (m) and Mencevax™ ACW at 24 to 30 m in Primed Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and reactogenicity of a booster dose of diphtheria-tetanus-whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b vaccine (DTPw-HBV/Hib) at 15-18 m and to assess the immunogenicity, safety, and reactogenicity of a dose of Mencevax™ Group A, C and W135 polysaccharide meningococcal vaccine (ACW) at 24 to 30 m in primed subjects. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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This open study will have two parallel groups based on the vaccination received in the primary study: AC primed Group: primed with Tritanrix™-HepB/Hib-MenAC vaccine and AC unprimed Group (control): primed with Tritanrix™-HepB/Hiberix™ vaccine. All subjects will receive a booster dose of Tritanrix™-HepB/Hiberix™ vaccine at 15 to 18 months of age with GSK Biological's OPV vaccine given concomitantly and a dose of Mencevax™ ACW vaccine at 24 to 30 months of age. Blood sampling will be done prior to (pre) and one month after (post) the Mencevax™ ACW vaccine administration for immunogenicity analyses. The study will last minimum 7 to maximum 16 months per subject. Mencevax™ ACWY was changed to Mencevax™ ACW throughout the posting to correct an inconsistency in the earlier version of the protocol posting and to reflect the actual situation.

Official Title
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Booster Vaccination Study to Assess Safety & Reactogenicity of a Dose of DTPw-HBV/Hib Vaccine and to Assess the Immunogenicity, Safety & Reactogenicity of a Dose of Mencevax™ ACW in Subjects Primed in Study 759346/007

Conditions
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Infections, Meningococcal

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


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 18 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 (CPMS N° 759346/007). 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. Booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib) and/or meningococcal serogroups A, C or W disease, after the date of the study conclusion visit of the primary vaccination study (CPMS N° 759346/007). History of diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A, C or W disease. Known exposure to diphtheria, tetanus, pertussis, hepatitis B, Hib and/or meningococcal serogroup A, C or W 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 vaccines administered in the study. 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. Axillary temperature ≥ 37.5°C at the time of vaccination. Administration of immunoglobulins and/or any blood products within the three months preceding the vaccination or planned administration during the study period. Anaphylactic reaction following the administration of vaccine in the primary vaccination study. Known hypersensitivity to any component of the vaccine, or subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, Hib or meningococcal vaccines.

Ages Eligible for Study
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Minimum Age: 15 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 |
| --- | --- |
| Experimental: AC primed Group<br> | Biological: Tritanrix™- HepB<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months<br>Biological: Hiberix™<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months<br>Biological: Mencevax™ ACW<br>* One subcutaneous dose during the booster vaccination study in subjects aged 24 to 30 months<br>|
| Active Comparator: AC unprimed Group<br> | Biological: Tritanrix™- HepB<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months<br>Biological: Hiberix™<br>* One intramuscular dose during the booster vaccination study in subjects aged 15 to 18 months<br>Biological: Mencevax™ ACW<br>* One subcutaneous dose during the booster vaccination study in subjects aged 24 to 30 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 Assay Against N. Meningitidis Serogroups A, C Using Rabbit Complement (rSBA-MenA,C) Antibodies | Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:128. | At one month post vaccination with Mencevax™ ACW vaccine (Month 25-31) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenA,C, W-135 Antibody Titers ≥ Predefined Cut-offs | Antibody titer cut-offs were ≥ 1:8 and ≥ 1:128. | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Anti-rSBA-MenA, C, W-135 Antibody Titers | Antibody titers were expressed as geometric mean titers (GMTs). | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA) and C (Anti-PSC) Antibody Concentrations Above Predefined Cut-off Values | Antibody concentrations cut-off were ≥ 0.3 and ≥2 micrograms per millilitre (µg/mL). | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Anti-PSA and Anti-PSC Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31 | 
| Number of Subjects With Anti- Polysaccharide W (Anti-PSW) Antibody Concentrations ≥ Predefined Cut-off Values | Antibody concentrations were ≥ 0.3 µg/mL. | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Anti-PSW Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). | Prior to (Months 24-30) & one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations ≥ Predefined Cut-off Values | Antibody concentrations cut-off were ≥ 10 milli international units per milliliter (mIU/mL). | Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs). | Prior to (Months 24-30) the administration of the Mencevax™ ACW vaccine | 
| Number of Subjects With Vaccine Response for rSBA-Men A, C and W-135 | Vaccine response was defined as follows: for initially seronegative subjects (i.e. with rSBA titre < 1:8 pre-vaccination), rSBA titre ≥ 1:32 post-vaccination (seroconversion), and for initially seropositive subjects (i.e. with rSBA titre ≥ 1:8 pre-vaccination), at least a 4-fold increase in rSBA titre from pre to post-vaccination. | At one month after the administration of the Mencevax™ ACW vaccine (Months 25-31) | 
| Number of Subjects With Fever | Any Fever (measured rectally) = subjects with symptom, regardless of the intensity grade. | During the 4-day (Days 0-3) after the administration of the Tritanrix™-HepB/Hiberix™ vaccine | 
| Number of Subjects With Solicited Local Symtoms | Assessed solicited local symptoms were: pain, redness and swelling at the injection site. Any = subjects with symptom, regardless of the intensity grade. | During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were: drowsiness, fever, irritability and loss of appetite. Any = subjects with symptoms, regardless of intensity grade and casual relationship to study vaccination. | During the 4-Day (Days 0-3) after the administration of the Mencevax™ ACW vaccine | 
| 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-Day (Days 0-30) after the administration of the Mencevax™ ACW vaccine | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Months 15-18 and up to Months 25-31 post vaccination | 

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