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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Tetanus; Diphtheria; Haemophilus Influenzae Type b; Whole Cell Pertussis; Diphtheria-Tetanus-Pertussis-Hepatitis B-Haemophilus Influenzae Type b-Neisseria Meningitidis Vaccin
• Intervention / Treatment: Biological: Tritanrix-HepB/Hib-MenAC; Biological: Mencevax ACWY; Biological: Tritanrix-HepB/Hiberix; Biological: Meningitec

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.

• Study Type: Interventional
• Enrollment (Actual): 617
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
  • Songkla, Thailand, 90110
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACAC GROUP; 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; Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Haemophilus influenzae Type b meningococcal AC-tetanus toxoid conjugate Vaccine
Experimental: ACHibPS GROUP; 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; GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine; Biological: Tritanrix-HepB/Hiberix; Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine
Experimental: HibACPS GROUP; 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; Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Haemophilus influenzae Type b meningococcal AC-tetanus toxoid conjugate Vaccine; Biological: Mencevax ACWY; GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine
Experimental: HibHibPS GROUP; 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; GSK Biologicals' Meningococcal serogroups A, C, W135 and Y polysaccharide vaccine; Biological: Tritanrix-HepB/Hiberix; Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine
Experimental: CC GROUP; 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; Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine; Biological: Meningitec; Wyeth's MenC CRM197 conjugated vaccine, Meningitec

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Primary Study

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2006
• Primary Completion (Actual): April 23, 2006
• Study Completion (Actual): April 23, 2006

Study Registration Dates

• First Submitted: August 26, 2005
• First Submitted That Met QC Criteria: August 26, 2005
• First Posted (Estimate): August 29, 2005

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Prophylaxis diphtheria; Hib & meningococcal serogroup A & C disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Neurologic Manifestations; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Orthomyxoviridae Infections; Clostridium Infections; Hypocalcemia; Calcium Metabolism Disorders; Corynebacterium Infections; Hepatitis B; Whooping Cough; Hepatitis; Hepatitis A; Influenza, Human; Tetanus; Diphtheria; Tetany
• Other Study ID Numbers: 104727 (Booster - 15-24 mths); 104730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 104727 (Booster - 15-24 mths)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register