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

Phase 3
Completed
Conditions
Haemophilus Influenzae Type b
Diphtheria-Tetanus-Pertussis-Hepatitis B-Haemophilus Influenzae Type b-Neisseria Meningitidis Vaccin
Whole Cell Pertussis
Hepatitis B
Diphtheria
Tetanus
Interventions
Biological: Tritanrix-HepB/Hib-MenAC
Biological: Mencevax ACWY
Biological: Tritanrix-HepB/Hiberix
Biological: Meningitec
Registration Number
NCT00136604
Lead Sponsor
GlaxoSmithKline
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
617
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HibACPS GROUPTritanrix-HepB/Hib-MenACSubjects 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
HibHibPS GROUPMencevax ACWYSubjects 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.
ACHibPS GROUPTritanrix-HepB/HiberixSubjects 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
HibACPS GROUPMencevax ACWYSubjects 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
ACAC GROUPTritanrix-HepB/Hib-MenACSubjects 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.
CC GROUPMeningitecSubjects 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.
ACHibPS GROUPMencevax ACWYSubjects 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
HibHibPS GROUPTritanrix-HepB/HiberixSubjects 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.
CC GROUPTritanrix-HepB/HiberixSubjects 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Subjects With Meningococcal C Serum Bactericidal Assay (SBA-MenC) Antibody Titers Above the Cut-off ValueOne month Post-Booster vaccination at 15-24 months of age

Pre-defined assay cut-off value for assessed titers was greater than or equal to (≥) 1:128.

Percentage of Seroprotected (SPR) Subjects With Anti-Polyribosyl Ribitol Phosphate Anti-(PRP) Antibody Concentrations Above the Cut-off ValueOne Month Post-Booster vaccination at 15-24 months of age

Antibody concentrations cut-off value was ≥ 1 microgram per milliliter (µg/mL).

Percentage of Subjects With SBA-MenA Antibody Titers Above the Cut-off ValueOne Month Post-Booster vaccination at 15-24 months of age

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).

Secondary Outcome Measures
NameTimeMethod
Percentage of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Above the Predefined Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations cut-off values were ≥ 0.3 and ≥ 2 micrograms per milliliter (µg/mL).

Anti-SBA-MenC Antibody TitersPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody titers were presented as geometric mean titers (GMTs).

Percentage of Subjects With Anti-polysaccharide A (Anti-PSA) Antibody Concentrations Above the Predefined Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations cut-off values were ≥ 0.3 and ≥ 2 micrograms per milliliter (µg/mL).

Number of Subjects With Any and Grade 3 Solicited Local SymptomsDuring the 4-day (Day 0 to Day 3) post-vaccination period

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.

Anti-PSA Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) ad expressed in micrograms per milliliter ().

Percentage of Seroprotected (SPR) Subjects With Anti-diphtheria Toxoid (Anti-DT) Antibody Concentrations Above the Predefined Cut-off ValuesOne month after (POST) the Booster vaccination at 15-24 months of age

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.

Anti-TT Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in international units per milliliter (IU/mL).

Percentage of SPR Subjects With Anti-(PRP) Antibody Concentrations Above Predefined Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations cut-off values were ≥ 0.15 and ≥ 1 micrograms per milliliter (µg/mL).

Anti-PRP Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL).

Percentage of Subjects With Serum Bactericidal Assay Against Meningococcal Serogroup A Using Rabbit Complement (rSBA-MenA) Antibody Titers Above the Pre-defined Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

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).

Anti-rSBA-MenA Antibody TitersPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody titers were presented as geometric mean titers (GMTs).

Anti-BPT Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL).

Percentage of Seroprotected (SPR) Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above the Predefined Cut-off ValuePrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations cut-off value was ≥ 10 international units per milliliter (IU/mL).

Anti-HBs Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).

Number of Subjects With Any, Grade 3 and Related Solicited General SymptomsDuring the 4-day (Days 0-3) post-vaccination period

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.

Percentage of Subjects With SBA-MenC Antibody Titers Above the Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Pre-defined assay cut-off values for assessed titers were greater than or equal to (≥) 1:8 and ≥ 1:128.

Anti-D Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in international units per milliliter (IU/mL).

Percentage of Seroprotected (SPR) Subjects With Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Above the Predefined Cut-off ValuesPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations cut-off value was ≥ 0.1 international units per milliliter (IU/mL).

Number of Subjects With Any Unsolicited Adverse Events (AEs)During the 31-day (Days 0-30) post-vaccination period

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.

Anti-PSC Antibody ConcentrationsPrior to (PRE) and one month after (POST) the Booster vaccination at 15-24 months of age

Antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in micrograms/milliliter (µg/ml).

Percentage of Seroprotected (SPR) Subjects With Anti-Bordetella Pertussis Toxoid (Anti-BPT) Antibody Concentrations Above the Predefined Cut-off ValueOne month Post-Booster vaccination

Antibody concentrations cut-off value was ≥ 15 ELISA units per milliliter (EL.U/mL).

Number of Subjects With Serious Adverse Events (SAEs)Up to one month Post-Booster vaccination

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.

Trial Locations

Locations (1)

GSK Investigational Site

🇹🇭

Songkla, Thailand

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