Impact of GSK Biologicals' 2189242A Vaccine on Nasopharyngeal Carriage, Safety & Immunogenicity in Children & Infants

• Occurrence of each grade 3 solicited local and general adverse event with relationship to vaccination (Cohort 1) [ Time Frame: Within 4 days (Day 0-Day 3) after vaccination ] [ Designated as safety issue: No ]
• Occurrence of grade 3 unsolicited adverse events with relationship to vaccination (Cohort 1) [ Time Frame: Within 31 days (Day 0-Day 30) after vaccination ] [ Designated as safety issue: No ]
• Occurrence of serious adverse events (SAEs) with relationship to vaccination (Cohort 1) [ Time Frame: From Day 0 to Day 30 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 1 month after dose 3 [ Time Frame: One (Month 3) month after dose 3 for Groups 3, 4, 5, 6 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 5 months after dose 3 [ Time Frame: Five (month 7) months after dose 3 for Groups 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 8 months after dose 3 [ Time Frame: Eight (month 10) months after dose 3 for Groups 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 1 month after dose 2 [ Time Frame: One (month 3) month after dose 2 for Groups 7, 8 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 5 months after dose 2 [ Time Frame: Five (month 7) months after dose 2 for Groups 7, 8 ] [ Designated as safety issue: No ]
• Occurrence of non-vaccine serotypes of S. pneumoniae in the nasopharynx (Cohort 2) - 3 months after dose 3 [ Time Frame: Three (month 10) months after dose 3 for Groups 7, 8 ] [ Designated as safety issue: No ]

• Occurrence of each solicited local and general adverse event (Cohort 1 and 2) [ Time Frame: Within 4 days (Day 0-Day 3) after vaccination ] [ Designated as safety issue: No ]
• Occurrence of any unsolicited adverse event (Cohort 1 and 2) [ Time Frame: Within 31 days (Day 0-Day 30) after vaccination ] [ Designated as safety issue: No ]
• Occurrence of any SAEs (Cohort 1) [ Time Frame: From Day 0 to Day 30 ] [ Designated as safety issue: No ]
• Occurrence of any SAEs (Cohort 1) [ Time Frame: From Day 0 to 180 ] [ Designated as safety issue: No ]
• Occurrence of any SAEs (Cohort 2) [ Time Frame: From Day 0 to Day 300 ] [ Designated as safety issue: No ]
• Occurrence of any specified haematological or biochemical abnormalities (Cohort 2) [ Time Frame: One month after vaccination (Month 1) ] [ Designated as safety issue: No ]
• Evaluation of the immune responses to the components of the investigational vaccine (Cohort 1) [ Time Frame: One month after vaccination (Month 1) ] [ Designated as safety issue: No ]
• Evaluation of the immune responses to the components of the investigational vaccine (Cohort 2) [ Time Frame: One, five and eight months after dose 3 (Months 3, 7 and 10) for Groups 3, 4, 5, 6 and one, five months after dose 2 (Months 3 and 7) and three months after dose 3 (Month 10) for Groups 7, 8. ] [ Designated as safety issue: No ]
• Evaluation of the immune responses to components of the co-administered DTPw-HBV/Hib vaccine and OPV vaccines (Cohort 2) [ Time Frame: One month after dose 3 (Month 3) ] [ Designated as safety issue: No ]
• Evaluation of the immune responses to components of the co-administered measles and yellow fever vaccines (Cohort 2) [ Time Frame: Three months after vaccination (Month 10) ] [ Designated as safety issue: No ]
• Occurrence of S. pneumoniae, H. influenzae and other bacterial pathogens in the nasopharynx (Cohort 2) [ Time Frame: One, five and eight months after dose 3 (Months 3, 7 and 10) for Groups 3, 4, 5, 6 and one, five months after dose 2 (Months 3 and 7) and three months after dose 3 (Month 10) for Groups 7 and 8. ] [ Designated as safety issue: No ]

This study will assess the impact on nasopharyngeal carriage, safety and immunogenicity of GSK Biologicals' pneumococcal vaccine 2189242A given as a 3-dose vaccination course and co-administered with other routine paediatric vaccines in infants in The Gambia. Two formulations containing different doses of pneumococcal antigen and two different schedules will be tested in infants.

There will be two cohorts in the study: Cohort 1 (children aged 2-4 years) and Cohort 2 (infants aged 8-10 weeks).

Before evaluating the two formulations of GSK Biologicals' pneumococcal vaccine 2189242A in infants (Cohort 2), safety and reactogenicity of the highest dose formulation of the vaccine will be evaluated in children aged 2 to 4 years (Cohort 1). Prevenar 13TM will be used as a control.

In the second step of the study, the two formulations of 2189242A will be tested in infants (Cohort 2). Both formulations of GSK Biologicals' pneumococcal vaccine 2189242A will be evaluated according to the Expanded Programme on Immunization (EPI) schedule i.e. a 2, 3, 4 months vaccination schedule, using licensed SynflorixTM and Prevenar 13 TM vaccines as comparators. The higher dose formulation of GSK Biologicals' pneumococcal vaccine 2189242A will be also evaluated according to the 2, 4, 9 months vaccination schedule using licensed SynflorixTM vaccine as comparator.

The study in infants will also assess the immune responses to routine vaccines when co-administered with the candidate pneumococcal vaccine, using licensed SynflorixTM and Prevenar 13™ vaccines as comparators.

• Pneumococcal Disease
• Haemophilus Influenzae Infections

• Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
  One dose (Group 1) or three doses (Groups 3 and 7) will be administered intramuscularly
• Other: Pneumococcal vaccine GSK2189242A (formulation 2)
  Three doses will be administered intramuscularly
• Biological: SynflorixTM
  Three doses will be administered intramuscularly
• Biological: Prevenar 13TM
  One dose (Group 2) or three doses (Group 6) will be administered intramuscularly
• Biological: TritanrixTM-HepB/Hib
  Three doses will be administered intramuscularly
• Biological: Polio SabinTM
  Three doses will be administered orally
• Biological: M-VacTM
  One dose will be administered intramuscularly
• Biological: StamarilTM
  One dose will be administered intramuscularly

• Experimental: Group 1 (Cohort 1)
  Children aged 2-4 yrs receiving pneumococcal vaccine GSK2189242A (formulation 1)
  Intervention: Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
• Active Comparator: Group 2 (Cohort 1)
  Children aged 2-4 yrs receiving Prevenar 13TM
  Intervention: Biological: Prevenar 13TM
• Experimental: Group 3 (Cohort 2)
  Infants (aged 8-10 weeks) receiving pneumococcal vaccine GSK2189242A (formulation 1) co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2, 3 and 4 months of age. M-VacTM and StamarilTM vaccines will be administered without any pneumococcal vaccine at 9 months of age.
  Interventions:

  • Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM
• Experimental: Group 4 (Cohort 2)
  Infants (aged 8-10 weeks) receiving pneumococcal vaccine GSK2189242A (formulation 2) co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2, 3 and 4 months of age. M-VacTM and StamarilTM vaccines will be administered without any pneumococcal vaccine at 9 months of age.
  Interventions:

  • Other: Pneumococcal vaccine GSK2189242A (formulation 2)
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM
• Active Comparator: Group 5 (Cohort 2)
  Infants (aged 8-10 weeks) receiving SynflorixTM co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2, 3 and 4 months of age. M-VacTM and StamarilTM vaccines will be administered without any pneumococcal vaccine at 9 months of age.
  Interventions:

  • Biological: SynflorixTM
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM
• Active Comparator: Group 6 (Cohort 2)
  Infants (aged 8-10 weeks) receiving Prevenar 13TM co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2, 3 and 4 months of age. M-VacTM and StamarilTM vaccines will be administered without any pneumococcal vaccine at 9 months of age.
  Interventions:

  • Biological: Prevenar 13TM
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM
• Experimental: Group 7 (Cohort 2)
  Infants (aged 8-10 weeks) receiving pneumococcal vaccine GSK2189242A (formulation 1) co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2 and 4 months followed by a third dose co-administered with M-VacTM and StamarilTM vaccines at approximately 9 months of age. The second doses of TritanrixTM-HepB/Hib and Polio SabinTM vaccines will be administered without any pneumococcal vaccine at 3 months of age.
  Interventions:

  • Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM
• Active Comparator: Group 8 (Cohort 2)
  Infants receiving SynflorixTM co-administered with TritanrixTM-HepB/Hib and Polio SabinTM vaccines at 2 and 4 months followed by a third dose co-administered M-VacTM and StamarilTM vaccines at approximately 9 months of age. The second doses of TritanrixTM-HepB/Hib and Polio SabinTM vaccines will be administered without any pneumococcal vaccine at 3 months of age.
  Interventions:

  • Biological: SynflorixTM
  • Biological: TritanrixTM-HepB/Hib
  • Biological: Polio SabinTM
  • Biological: M-VacTM
  • Biological: StamarilTM

Inclusion Criteria:

Inclusion criteria for subjects in Cohort 1 (children) and Cohort 2 (infants):

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol

• Male or female between, and including,

  • 2 to 4 years of age at the time of the first vaccination for subjects in Cohort 1 (children).
  • 8 to 10 weeks (56-76 days) of age at the time of the first vaccination for subjects in Cohort 2 (infants).
• Signed or thumb-printed informed consent obtained from the parents/LAR(s) of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Permanent residence in the study area and no intention of leaving during the study period.

Additional inclusion criteria for subjects in Cohort 1:

• Previously completed three-dose primary course of diphtheria-tetanus-pertussis (DTP) vaccination.

Exclusion Criteria:

Exclusion criteria for subjects in Cohort 1 (children) and Cohort 2 (infants):

• Child in care.
• Use of any investigational or non-registered product 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 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 during the study period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the exception of licensed flu vaccines.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product
• Previous vaccination against S. pneumoniae.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Malnutrition
• A family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
• Major congenital defects or any chronic illness.
• History of any neurologic disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Administration of immunoglobulins and/ or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Contraindications to any co-administered vaccine.
• Any medical condition that would contraindicate the initiation of routine immunization outside a clinical trial context.

Additional exclusion criteria for subjects in Cohort 1:

• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b with the exception of vaccines where the first dose should be given within the first two weeks of life according to the national recommendations (for example Bacillus Calmette-Guérin [BCG] and hepatitis B vaccination).

• Program for Appropriate Technology in Health
• Department of State for Health and Social Welfare, The Gambia
• Medical Research Council Unit, The Gambia
• London School of Hygiene and Tropical Medicine