Safety Study of Tritanrix-HepB/Hib-MenAC, Tritanrix-HepB/Hiberix, and Mencevax ACWY Vaccines in Children

Study Overview
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Brief Summary
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This study will be conducted in two stages. In the diphtheria, tetanus, pertussis (DTP) booster phase, subjects will receive a booster dose of Tritanrix-HepB/Hib-MenAC or Tritanrix-HepB/Hiberix (active control) at 15 to 18 or 24 months in a single-blind manner so that the subjects' parents will not know which vaccine was administered to their child. In the Mencevax ACWY phase at 24-30 months, a dose of Mencevax ACWY will be given in an open manner to only those subjects who received less than 4 doses of Tritanrix-HepB/Hib-MenAC. No blood samples will be taken in this safety study.

Detailed Description
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Subjects previously primed with Tritanrix-HepB/Hib-MenAC will receive Tritanrix-HepB/Hib-MenAC or Tritanrix-HepB/Hiberix vaccine (at 15-18/24 m), respectively, without or with Mencevax ACWY vaccine at 24 to 30 months of age. Subjects previously primed with Tritanrix-HepB/Hiberix will receive Tritanrix-HepB/Hib-MenAC or Tritanrix-HepB/Hiberix vaccine (at 15-18/24 m) with Mencevax ACWY vaccine at 24 to 30 months of age.

Official Title
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Assess Reactogenicity & Safety of a Booster of Either Tritanrix-HepB/Hib-MenAC or Tritanrix-HepB/Hiberix Given (Single-blind) at 15-18 (Philippines)/15-24 Mths (Thailand) & a Dose of Mencevax ACWY at 24-30 Mths (Open Label)

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

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the parent or guardian of a healthy male or female child between, and including 15 and 18 months age (Philippines)/ 15 and 24 months age (Thailand) at the time of vaccination and who have previously received a 3-dose primary vaccination in the studies DTPwHB/HibMenAC-TT-004 (CPMS No. 759346/004) or DTPW-HBV=HIB-MENAC-TT-013 (eTrack No. 100791). 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 (> 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. Note: Oral poliovirus vaccine can be given concomitantly. Booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b (Hib) and/or meningococcal serogroups A and C disease, after the date of the study conclusion visit of the primary vaccination study.

Ages Eligible for Study
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Minimum Age: 427 Days
Maximum Age: 577 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_Thailand Group<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine in the primary study ( NCT00317187) are boosted in the current study with one dose of the same vaccines at 15 to 24 months (Thailand) 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_Thailand Group<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine in the primary study (NCT00317187) are boosted in the current study with one dose of Tritanrix-HepB/Hiberix at 15 to 24 months (Thailand) 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/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>Biological: Mencevax-ACWY<br>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|
| Experimental: HibACPS_Thailand Group<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317187) are boosted in the current study with one dose of Trianrix-Hepb co-administrated with Hib-MenAC-TT vaccine at 15 to 24 months (Thailand) 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>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|
| Experimental: HibHibPS_Thailand Group<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317187) are boosted in the current study with one dose of the same vaccine at 15 to 24 months (Thailand) 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/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>Biological: Mencevax-ACWY<br>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|
| Experimental: ACAC_Philippines Group<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine in the primary study (NCT00317135) are boosted in the current study with one dose of the same vaccines at 15 to 18 months (Philippines) 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_Philippines Group<br>Subjects vaccinated with 3 doses of Tritanrix-Hepb co-administrated with Hib-MenAC-TT vaccine in the primary study (NCT00317135) are boosted in the current study with one dose of Tritanrix-HepB/Hiberix at 15 to 18 months (Philippines) 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/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>Biological: Mencevax-ACWY<br>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|
| Experimental: HibACPS_Philippines Group<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317135) are boosted in the current study with one dose of Trianrix-Hepb co-administrated with Hib-MenAC-TT vaccine at 15 to 18 months (Philippines) 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>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|
| Experimental: HibHibPS_Philippines Group<br>Subjects vaccinated with 3 doses of Tritanrix-HepB/Hiberix vaccine in the primary study (NCT00317135) are boosted in the current study with one dose of the same vaccine at 15 to 18 months (Philippines) 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/Hiberix<br>* Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B Vaccine, Haemophilus influenzae type b conjugate vaccine<br>Biological: Mencevax-ACWY<br>* Meningococcal Serogroups A, C, W-135 and Y Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Fever >39°C (Rectal Route). | Among solicited general symptoms fever [defined as rectal temperature equal to or above (≥) 38 degrees Celsius (°C )] was assessed, post vaccination. Grade 3 fever = fever > 39.0 °C. | During the 4-day (Day 0-3) follow-up period after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms, Other Than Fever > 39.0°C | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Day 0-3) follow-up period after vaccination | 
| 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 0-3) follow-up period after booster vaccination | 
| 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 (Day 0-30) following booster vaccination | 
| 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 15 to 18 months or 15 to 24 months of age and up to 25 to 31 months of age post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hib & Neisseria meningitidis serogroups A & C diseases