Response to GSK Biologicals' Tritanrix-HepB/Hib-MenAC Vacc (4th Dose) at 15-24m & Mencevax ACWY at 24-30m

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the immunogenicity, safety and reactogenicity of a booster dose of DTPw-HBV/Hib-MenAC compared to DTPw-HBV/Hib given to healthy subjects at 15 to 24 months of age primed with 3 doses of Tritanrix-HepB/Hib-MenAC in study 100480. Antibody persistence will be evaluated at 24 to 30 months. Immunogenicity, safety and reactogenicity of a dose of Mencevax ACWY given at 24 to 30 months will also be evaluated when given to subjects not boosted with a MenA conjugate and/or MenC containing vaccine.

Detailed Description
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This study will be conducted in two stages. In the DTP booster phase subjects will receive a booster dose of Tritanrix-HepB/Hib-MenAC or Tritanrix-HepB/Hib (active control) at 15 to 24 months in a single-blind manner so that the subjects' parents will not know which vaccine was administered to their child (this booster phase is no longer recruiting). In the Mencevax ACWY phase at 24-30 months a dose of Mencevax ACWY will be given to subjects who were not boosted with a MenA conjugate and/or MenC containing vaccine at 15-24 months in an open manner (this booster phase is not yet recruiting). Up to four blood samples will be taken: before and one month after the administration of the DTP booster dose and of Mencevax ACWY. To comply with the immunisation calender of Thailand, at 15-24 months all subjects will receive OPV. At 16-25 months 2 doses of Japanese Encephalitis (JE) vaccine or a dose of varicella vaccine will be offered and at 25-31 months a dose of varicella or JE vaccine will be offered.

Official Title
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Assess Immunogenicity, Safety & Reactogenicity of a 4th Dose of GSK Biologicals' Tritanrix-HepB/Hib-MenAC at 15-24 m & of a Dose of Mencevax ACWY at 24-30 m in Subjects Primed With 3 Doses of Tritanrix-HepB/Hib-MenAC

Conditions
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Whole Cell Pertussis, Haemophilus Influenzae Type b, Hepatitis B, Diphtheria, Tetanus, Diphtheria-Tetanus-Pertussis-Hepatitis B-Haemophilus Influenzae Type b-Neisseria Meningitidis Vaccin

Intervention / Treatment
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* Biological: Tritanrix-HepB/Hib-MenAC
* Biological: Mencevax ACWY
* Biological: Tritanrix-HepB/Hiberix
* Biological: Meningitec


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male or female between and including 15 and 24 months of age Having participated in the primary vaccination study DTPW-HBV=HIB-MENAC-TT-003 (eTrack No. 100480) Exclusion criteria: Booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib) and/or meningococcal serogroups A and/or C disease not foreseen in the protocol, after the date of the study conclusion visit of the primary vaccination study DTPW-HBV=HIB-MENAC-TT-003 (eTrack No. 100480). History of or 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. A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures including febrile seizures (at least two events) in infancy.

Ages Eligible for Study
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Minimum Age: 427 Days
Maximum Age: 730 Days

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACAC GROUP<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine in the primary study (NCT00317161) are boosted in the current study with one dose of the same vaccines at 15 to 24 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. No Mencevax ACWY vaccine at 24 to 30 months of age. | Biological: Tritanrix-HepB/Hib-MenAC<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Haemophilus influenzae Type b meningococcal AC-tetanus toxoid conjugate Vaccine<br>|
| Experimental: ACHibPS GROUP<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with MenAC-TT vaccine in the primary study (NCT00317161) are boosted in the current study with one dose of Tritanrix-HepB/Hiberix at 15 to 24 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. Subjects are also administered one booster dose of Mencevax ACWY vaccine at 24 to 30 months of age by deep subcutaneous injection in the upper region of the left arm | Biological: Mencevax ACWY<br>* GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine<br>Biological: Tritanrix-HepB/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>|
| Experimental: HibACPS GROUP<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317161) are boosted in the current study with one dose of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine at 15 to 24 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. Subjects are also administered one booster dose of Mencevax ACWY vaccine at 24 to 30 months of age by deep subcutaneous injection in the upper region of the left arm | Biological: Tritanrix-HepB/Hib-MenAC<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Haemophilus influenzae Type b meningococcal AC-tetanus toxoid conjugate Vaccine<br>Biological: Mencevax ACWY<br>* GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine<br>|
| Experimental: HibHibPS GROUP<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317161) are boosted in the current study with one dose of the same vaccine at 15 to 24 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. Subjects are also administered one booster dose of Mencevax ACWY vaccine at 24 to 30 months of age by deep subcutaneous injection in the upper region of the left arm. | Biological: Mencevax ACWY<br>* GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine<br>Biological: Tritanrix-HepB/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>|
| Experimental: CC GROUP<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix + Meningitec vaccine in the primary study (NCT00317161) are boosted in the current study with one dose of the same vaccine at 15 to 24 months of age, intramuscularly into the anterolateral quadrant of the left thigh or upper region of the left arm. No Mencevax ACWY vaccine at 24 to 30 months of age. | Biological: Tritanrix-HepB/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>Biological: Meningitec<br>* Wyeth's MenC CRM197 conjugated vaccine, Meningitec<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Meningococcal C Serum Bactericidal Assay (SBA-MenC) Antibody Titers Above the Cut-off Value | Pre-defined assay cut-off value for assessed titers was greater than or equal to (≥) 1:128. | One month Post-Booster vaccination at 15-24 months of age | 
| Percentage of Subjects With SBA-MenA Antibody Titers Above the Cut-off Value | Pre-defined assay cut-off value for assessed titers was greater than or equal to (≥) 1:128. Note: For the MenA antibodies with assay on SBA, additional testing were done using a serogroup A strain 3125 (L10 immunotype). | One Month Post-Booster vaccination at 15-24 months of age | 
| Percentage of Seroprotected (SPR) Subjects With Anti-Polyribosyl Ribitol Phosphate Anti-(PRP) Antibody Concentrations Above the Cut-off Value | Antibody concentrations cut-off value was ≥ 1 microgram per milliliter (µg/mL). | One Month Post-Booster vaccination at 15-24 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of SPR Subjects With Anti-(PRP) Antibody Concentrations Above Predefined Cut-off Values | Antibody concentrations cut-off values were ≥ 0.15 and ≥ 1 micrograms per milliliter (µg/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Subjects With SBA-MenC Antibody Titers Above the Cut-off Values | Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:8 and ≥ 1:128. | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-SBA-MenC Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Subjects With Serum Bactericidal Assay Against Meningococcal Serogroup A Using Rabbit Complement (rSBA-MenA) Antibody Titers Above the Pre-defined Cut-off Values | Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:8 and (≥) 1:128. Note: For the MenA antibodies with assay on SBA, additional testing were done using a serogroup A strain 3125 (L10 immunotype). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-rSBA-MenA Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Above the Predefined Cut-off Values | Antibody concentrations cut-off values were ≥ 0.3 and ≥ 2 micrograms per milliliter (µg/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-PSC Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in micrograms/milliliter (µg/ml). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Subjects With Anti-polysaccharide A (Anti-PSA) Antibody Concentrations Above the Predefined Cut-off Values | Antibody concentrations cut-off values were ≥ 0.3 and ≥ 2 micrograms per milliliter (µg/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-PSA Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) ad expressed in micrograms per milliliter (). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Seroprotected (SPR) Subjects With Anti-diphtheria Toxoid (Anti-DT) Antibody Concentrations Above the Predefined Cut-off Values | Antibody concentrations cut-off values were ≥ 0.1 international units per milliliter (IU/mL) as assessed by enzyme-linked immunosorbent assay (ELISA) or ≥ 0.016 IU/ml as assessed by Vero cell neutralization test if concentrations were < 0.1 IU/ml when assessed by ELISA. | One month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-D Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in international units per milliliter (IU/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Seroprotected (SPR) Subjects With Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Above the Predefined Cut-off Values | Antibody concentrations cut-off value was ≥ 0.1 international units per milliliter (IU/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-TT Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in international units per milliliter (IU/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Seroprotected (SPR) Subjects With Anti-Bordetella Pertussis Toxoid (Anti-BPT) Antibody Concentrations Above the Predefined Cut-off Value | Antibody concentrations cut-off value was ≥ 15 ELISA units per milliliter (EL.U/mL). | One month Post-Booster vaccination | 
| Anti-BPT Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Percentage of Seroprotected (SPR) Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above the Predefined Cut-off Value | Antibody concentrations cut-off value was ≥ 10 international units per milliliter (IU/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). | Prior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. | During the 4-day (Day 0 to Day 3) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite, fever [defined as axillary temperature equal to or above 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any 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) post-vaccination period | 
| 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. | Up to one month Post-Booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylaxis diphtheria, Hib & meningococcal serogroup A & C disease