Safety & Immunogenicity of 1 Dose of GSK134612 in Children 12-14 Mths and 3-5 Yrs Old

• Meningococcal SBA titres [ Time Frame: Prior to & 1 mth after the 1st dose, in all subjects; & 12 mths after priming, in all subjects of Group E & the group with the selected MenACWY-TT formulation; & 1 mth after the admin of the booster dose, in subjects who receive the booster dose ] [ Designated as safety issue: No ]
• Anti-meningococcal polysaccharide concentrations [ Time Frame: Prior to & 1 mth after the 1st dose, in all subjects; & 12 mths after priming, in all subjects of Group E & the group with the selected MenACWY-TT formulation; & 1 mth after the admin of the booster dose, in subjects who receive the booster dose ] [ Designated as safety issue: No ]
• Anti-tetanus toxoid seropositivity and antibody concentrations [ Time Frame: Prior to & one month after the first vaccine dose, in all subjects ] [ Designated as safety issue: No ]
• Occurrence of local and general solicited adverse events [ Time Frame: During the 8-day follow-up period following administration of each vaccine dose ] [ Designated as safety issue: No ]
• Occurrence of unsolicited adverse events [ Time Frame: During the 31-day follow-up period following administration of each vaccine dose ] [ Designated as safety issue: No ]
• Occurrence of any serious adverse events [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of one dose of four different formulations of the MenACWY conjugate vaccine when given to healthy children aged 12-14 months and 3-5 years. The selection of the best formulation will be based on data obtained up to one month after the vaccine dose.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

The study will enrol subjects of 12 to 14 months of age and subjects of 3 to 5 years of age. 3 formulations of GSK's MenACWY conjugate vaccine will be administered in a double-blind manner, while the 4th one will be single-blinded. Administration of the candidate vaccine or the active controls (MenC-CRM197 or Mencevax™ ACWY) will be done in an open manner. The study will be conducted in two stages: The primary vaccination phase (Study Stage 1) of the study will include all subjects; the second (booster/persistence) phase of the study (Study Stage 2) will include subjects in the active control groups and in the group which was primed with the selected MenACWY formulation.

The study will be conducted in a double-blind manner for groups receiving formulations A, B, C and in single blind manner with respect to the group receiving formulation D. The control vaccines will be administered in an open manner with respect to the investigational vaccination regimens.

Each group will have one blood sample prior to and one blood sample one month after the first vaccine dose.

• Biological: Conjugated meningococcal ACWY-TT (vaccine)
  One intramuscular dose during the primary vaccination
• Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age, in Greece only
• Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
  One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age, in Austria only
• Biological: Meningitec™
  One intramuscular dose during the primary vaccination study in subjects of 12-24 months of age
• Biological: Mencevax™ACWY
  One subcutaneous dose during the primary vaccination study in subjects of 3-5 years of age (Group E) and intramuscular administration of 1/5 dose during the booster vaccination study in subjects of 12-14 months of age (Groups A and E)

• Experimental: Group A
  Subjects of 12-14 months of age or 3-5 years of age who will receive formulation A
  Interventions:

  • Biological: Conjugated meningococcal ACWY-TT (vaccine)
  • Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  • Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
  • Biological: Mencevax™ACWY
• Experimental: Group B
  Subjects of 12-14 months of age or 3-5 years of age who will receive formulation B
  Interventions:

  • Biological: Conjugated meningococcal ACWY-TT (vaccine)
  • Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  • Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
• Experimental: Group C
  Subjects of 12-14 months of age or 3-5 years of age who will receive formulation C
  Interventions:

  • Biological: Conjugated meningococcal ACWY-TT (vaccine)
  • Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  • Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
• Experimental: Group D
  Subjects of 12-14 months of age or 3-5 years of age who will receive formulation D
  Interventions:

  • Biological: Conjugated meningococcal ACWY-TT (vaccine)
  • Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  • Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
• Active Comparator: Group E
  Subjects of 12-14 months of age who will receive MenC-CRM197 and subjects of 3-5 years of age who will receive Mencevax™ ACWY
  Interventions:

  • Biological: DTPa-IPV/Hib vaccine (Infanrix™-IPV/Hib)
  • Biological: DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™)
  • Biological: Meningitec™
  • Biological: Mencevax™ACWY

Inclusion criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including 12 and 14 months or 3 and 5 years of age at the time of the first vaccination.
• Written informed consent obtained from the parent or guardian of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Previously completed routine childhood vaccinations to the best of his/her parents'/guardians' knowledge. For pertussis vaccination, the children aged 12-14 months should have been vaccinated with an acellular pertussis vaccine.

Exclusion criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the first dose of vaccine and up to one month after administration of each study vaccine dose with the exception of oral polio vaccine (OPV).
• Previous vaccination against meningococcal serogroup A, C, W-135 or Y disease.
• Administration of a H. influenzae type b, diphtheria or tetanus vaccine within 3 months before the first dose of vaccine.

• For subjects aged 12-14 months at enrolment:

  • For Austria: DTPa-HBV-IPV/Hib booster vaccination in the second year of life: these booster vaccines will be given at Visit 2.
  • For Greece: DTPa-IPV/Hib booster vaccination in the second year of life: these booster vaccines will be given at Visit 2.
• History of meningococcal serogroup A, C, W-135 or Y disease.
• Known exposure to meningococcal serogroup A, C, W-135 or Y disease within the previous year.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.