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

Phase 3

Completed

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

Interventions: Biological: Tritanrix-HepB/Hib-MenAC
Biological: Tritanrix-HepB/Hiberix
Biological: Mencevax-ACWY

Registration Number: NCT00228917

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 798

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACHibPS_Thailand Group	Mencevax-ACWY	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
HibACPS_Thailand Group	Mencevax-ACWY	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
HibACPS_Thailand Group	Tritanrix-HepB/Hib-MenAC	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
HibACPS_Philippines Group	Tritanrix-HepB/Hib-MenAC	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
ACAC_Thailand Group	Tritanrix-HepB/Hib-MenAC	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
ACHibPS_Thailand Group	Tritanrix-HepB/Hiberix	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
HibHibPS_Thailand Group	Tritanrix-HepB/Hiberix	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
HibHibPS_Thailand Group	Mencevax-ACWY	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
ACAC_Philippines Group	Tritanrix-HepB/Hib-MenAC	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
ACHibPS_Philippines Group	Mencevax-ACWY	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
ACHibPS_Philippines Group	Tritanrix-HepB/Hiberix	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
HibACPS_Philippines Group	Mencevax-ACWY	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
HibHibPS_Philippines Group	Tritanrix-HepB/Hiberix	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
HibHibPS_Philippines Group	Mencevax-ACWY	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

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Fever >39°C (Rectal Route).	During the 4-day (Day 0-3) follow-up period after booster vaccination	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.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Serious Adverse Events (SAEs).	From 15 to 18 months or 15 to 24 months of age and up to 25 to 31 months of age post 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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms, Other Than Fever > 39.0°C	During the 4-day (Day 0-3) follow-up period after vaccination	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.	During the 4-day (Day 0-3) follow-up period after booster vaccination	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.
Number of Subjects With Any Unsolicited Adverse Events (AEs).	During the 31-day (Day 0-30) following booster vaccination	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.