Clinical trial NCT01262872: Impact of GSK Biologicals' 2189242A Vaccine on Nasopharyngeal Carriage, Safety & Immunogenicity in Children & Infants
Official title: Impact of GSK Biologicals' 2189242A Vaccine on Nasopharyngeal Carriage, Safety and Immunogenicity When Co-administered With Routine EPI Vaccines in Infants Following Safety Assessment in Children Aged 2-4 Years in The Gambia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Streptococcal
Keywords: Haemophilus influenzae
Streptococcus pneumoniae
The Gambia
immunogenicity
nasopharyngeal carriage
infants
safety
Pneumococcal vaccine
children
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: PATH
name: Department of State for Health and Social Welfare, The Gambia
name: Medical Research Council Unit, The Gambia
name: London School of Hygiene and Tropical Medicine
First posted: 2010-12-17
Enrollment: 1320
Sex: ALL
Minimum age (years): 56
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: There will be two cohorts in the study: Cohort 1 (children aged 2-4 years) and Cohort 2 (infants aged 8-10 weeks), and two steps in the study, Step 1 and Step 2. Step 1 will consist in a safety evaluation of the GSK Biologicals' pneumococcal vaccine 2189242A (GSK 2189242A or 10PP vaccine). Before evaluating the two formulations of the 10PP vaccine in infants (Cohort 2), safety and reactogenicity of the highest dose formulation of this vaccine will be evaluated in children (Cohort 1). Prevnar 13™ will be used as a control. In the second step of the study, Step 2, two investigational formulations of the 10PP vaccine will be tested in infants (Cohort 2) as regards immunogenicity, reactogenicity and safety. Both formulations of the 10PP vaccine will be evaluated according to the Expanded Programme on Immunization (EPI) schedule i.e. a 2, 3, 4 months vaccination schedule, using licensed Synflorix™ and Prevnar 13™ vaccines as comparators. The higher dose (HD) formulation of the 10PP vaccine will be also evaluated according to the 2, 4, 9 months vaccination schedule using licensed Synflorix™ 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 Synflorix™ and Prevnar 13™ vaccines as comparators.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms and Grade 3 Solicited Local Symptoms With Relationship to Vaccination - For Step 1/Cohort 1 Subjects
timeFrame: Within the 4-day (Days 0-3) period post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms With and Without Relationship to Vaccination - For Step 1/Cohort 1 Subjects
timeFrame: Within the 4-day (Days 0-3) period post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Number of Subjects With Any and Grade 3 Unsolicited Adverse Events (AEs) With and Without Relationship to Vaccination - In Step 1/Cohort 1 Subjects
timeFrame: Within the 31-day (Days 0-30) period post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Number of Subjects With Any Serious Adverse Events (SAEs) and With SAE(s) With Relationship to Vaccination - In Step 1/Cohort 1 Subjects
timeFrame: From Day 0 to Month 1
measure: Number of Subjects With Non-vaccine Serotypes of Streptococcus Pneumoniae (S. pn.) in the Nasopharynx - For Cohort 2/Step 2, Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Non-vaccine Serotypes of Streptococcus Pneumoniae (S. pn.) in the Nasopharynx - For Cohort 2/Step 2, Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
Secondary outcomes:
measure: Number of Subjects With Haematological or Biochemical Abnormalities With Respect to Normal Laboratory Ranges - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Number of Subjects With Serious Adverse Events (SAEs) - For Step 1/Cohort 1 Subjects
timeFrame: From Day 0 to Month 6
measure: Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (Ply) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Antibody Concentrations Against Protein D (PD) - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotypes 3, 6A and 19A - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotype 6C - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 3, 6A and 19A - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotype 6C - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid (Ply) Haemolysis Activity, or Hem-Ply Antibodies - For Cohort 1/Step 1 Subjects
timeFrame: At Month 1, or 1 month post vaccination with pneumococcal vaccine (10PP vaccine or Prevnar 13™)
measure: Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (Ply) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (Ply) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Concentrations Against Protein D (PD) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Protein D (PD) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Concentrations Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 2/Step 2 Subjects Who Received the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 2/Step 2 Subjects Who Received the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Concentrations Against Vaccine Serotypes 3 and 19A - For Cohort 2/Step 2 Subjects Who Received the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotypes 3 and 19A - For Cohort 2/Step 2 Subjects Who Received the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Concentrations Against Vaccine Serotype 6A - For Cohort 2/Step 2 Subjects Who Received the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotype 6A - For Cohort 2/Step 2 Subjects Who Received the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Concentrations Against Vaccine Serotype 6C - For Cohort 2/Step 2 Subjects Who Received the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Concentrations Against Vaccine Serotype 6C - For Cohort 2/Step 2 Subjects Who Received the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 3 and 6A - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotypes 3 and 6A - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotype 19A - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotype 19A - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotype 6C - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Titers for Opsonophagocytic Activity Against Vaccine Serotype 6C - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid (Ply) Haemolysis Activity, or Hem-Ply Antibodies - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid (Ply) Haemolysis Activity, or Hem-Ply Antibodies - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1 month post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 month post-Dose 2 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Against Bordetella Pertussis (Anti-BPT) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1 month post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Concentrations of Antibodies Against Bordetella Pertussis (Anti-BPT) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 month post-Dose 2 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1 month post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 month post-Dose 2 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Against Hepatitis B Surface Antigens (Anti-HBs) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1 month post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Concentrations of Antibodies Against Hepatitis B Surface Antigens (Anti-HBs) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 month post-Dose 2 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Antibody Titers Against Poliovirus 1, 2 and 3 (Anti-Polio, Anti-Polio 2 and Anti-Polio 3) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1 month post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Antibody Titers Against Poliovirus 1, 2 and 3 (Anti-Polio, Anti-Polio 2 and Anti-Polio 3) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 month post-Dose 2 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Concentrations of Antibodies Against Measles (Anti-Measles) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 3 months (Mth) post-vaccination with Stamaril™/M-Vac™
measure: Concentrations of Antibodies Against Measles (Anti-Measles) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 3 months (Mth) post-vaccination with Stamaril™/M-Vac™
measure: Titers of Antibodies Against Yellow Fever (Anti-YF) - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 3 months (Mth) post-vaccination with Stamaril™/M-Vac™
measure: Titers of Antibodies Against Yellow Fever (Anti-YF) - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 3 months (Mth) post-vaccination with Stamaril™/M-Vac™
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - For Cohort2/Step 2 Subjects Receiving the 3+0 Schedule.
timeFrame: Within the 4-day (Days 0-3) periods post vaccination with 3 doses of pneumococcal vaccine (10PP vaccine, Synflorix™ or Prevnar 13™), across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - For Cohort2/Step 2 Subjects Receiving the 2+1 Schedule.
timeFrame: Within the 4-day (Days 0-3) periods post vaccination with the 2 first doses of pneumococcal vaccine (10PP vaccine or Synflorix™), across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - For Cohort2/Step 2 Subjects Receiving the 2+1 Schedule.
timeFrame: Within the 4-day (Days 0-3) period post vaccination with Dose 3 of pneumococcal vaccine (10PP vaccine or Synflorix™)
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination - For Step 2/Cohort 2 Subjects Receiving the 3+0 Schedule
timeFrame: Within the 4-day (Days 0-3) periods post vaccination with 3 doses of pneumococcal vaccine (10PP vaccine, Synflorix™ or Prevnar 13™), across doses
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination - For Step 2/Cohort 2 Subjects Receiving the 2+1 Schedule
timeFrame: Within the 4-day (Days 0-3) periods post vaccination with the 2 first doses of pneumococcal vaccine (10PP vaccine or Synflorix™), across doses
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination - For Step 2/Cohort 2 Subjects Receiving the 2+1 Schedule
timeFrame: Within the 4-day (Days 0-3) period post vaccination with Dose 3 of pneumococcal vaccine (10PP vaccine or Synflorix™)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - For Step 2/Cohort 2 Subjects Receiving the 3+0 Schedule
timeFrame: Within the 31-day (Days 0-30) periods post vaccination with 3 doses of pneumococcal vaccine (10PP vaccine, Synflorix™ or Prevnar 13™), across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - For Step 2/Cohort 2 Subjects Receiving the 2+1 Schedule
timeFrame: Within the 31-day (Days 0-30) periods post vaccination with the first 2 doses of pneumococcal vaccine (10PP vaccine or Synflorix™), across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - For Step 2/Cohort 2 Subjects Receiving the 2+1 Schedule
timeFrame: Within the 31-day (Days 0-30) period post vaccination with Dose 3 of pneumococcal vaccine (10PP vaccine or Synflorix™)
measure: Number of Subjects With Any Serious Adverse Events (SAEs) - For Step 2/Cohort 2 Subjects Receiving the 3+0 Schedule
timeFrame: From Day 0 to Month 10
measure: Number of Subjects With Any Serious Adverse Events (SAEs) - For Step 2/Cohort 2 Subjects Receiving the 2+1 Schedule
timeFrame: From Day 0 to Month 10
measure: Number of Subjects With Streptococcus Pneumoniae (Any) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Streptococcus Pneumoniae (Any) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Streptococcus Pneumoniae (10Pn-PD-DiT Vaccine Serotypes) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Streptococcus Pneumoniae (10Pn-PD-DiT Vaccine Serotypes) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Streptococcus Pneumoniae (Synflorix Related Serotypes) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Streptococcus Pneumoniae (Synflorix Related Serotypes) in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Haemophilus Influenzae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Haemophilus Influenzae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Moraxella Catarrhalis in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Moraxella Catarrhalis in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Group A Streptococcus in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Group A Streptococcus in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Staphylococcus Aureus in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine, Synflorix™ or Prevnar 13™)
measure: Number of Subjects With Staphylococcus Aureus in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Non-vaccine Serotypes/Serogroups of Streptococcus Pneumoniae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Non-vaccine Serotypes/Serogroups of Streptococcus Pneumoniae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Any New Streptococcus Pneumoniae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Any New Streptococcus Pneumoniae in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Haemophilus Influenzae Strains Identified With Polymerase Chain Reaction Differentiation in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 3+0 Schedule
timeFrame: At 1, 5 and 8 months (Mth) post-Dose 3 of pneumococcal vaccine administered (10PP vaccine or Synflorix™)
measure: Number of Subjects With Acquisition of Haemophilus Influenzae Strains Identified With Polymerase Chain Reaction Differentiation in the Nasopharynx - For Cohort 2/Step 2 Subjects Receiving the 2+1 Schedule
timeFrame: At 1 and 5 months (Mth) post-Dose 2, and at 3 months post-Dose 3 of the pneumococcal vaccine administered (10PP vaccine or Synflorix™)
Other outcomes:
measure: Description of Non-Vaccine-Type S.Pneumoniae Samples Isolated From Nasopharyngeal Swabs Before and After Vaccination for the Ply Gene - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) or at Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
measure: Description of Non-Vaccine-Type S.Pneumoniae Samples Isolated From Nasopharyngeal Swabs Before and After Vaccination for the PhtD Gene - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) or at Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
measure: Number of Samples With Ply Protein Variants Classified by Number of Amino Acids (AA) Mutation Versus Vaccine Sequence in a Subset of Non-Vaccine-Type S.Pneumoniae Isolates From Nasopharyngeal Swabs - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) and Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
measure: Percentage (Median and Mean) of Protein Identity Relative to Amino Acid Sequence of Ply Protein in the Vaccine for a Subset of Non-Vaccine-Type S.Pneumoniae Isolates From Nasopharyngeal Swabs - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) and Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
measure: Number of Samples With PhtD Protein Variants in a Subset of Non-Vaccine-Type S.Pneumoniae Isolates From Nasopharyngeal Swabs - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) and Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
measure: Percentage (Median and Mean) of Protein Identity Relative to Amino Acid Sequence of PhtD Protein in the Vaccine for a Subset of Non-Vaccine-Type S.Pneumoniae Isolates From Nasopharyngeal Swabs - Cohort 2
timeFrame: At Month 0 (Pre-vaccination), Month 3 (1 month [m] post-dose [P] III-3+0 schedule or PII-2+1 schedule), Month 7 (5 m PIII - 3+0 schedule or PII-2+1 schedule) and Month 10 (8 m PIII - 3+0 schedule or 3 m post-booster-2+1 schedule)
Locations:
city: Banjul
country: Gambia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Odutola A, Antonio M, Owolabi O, Bojang A, Foster-Nyarko E, Donkor S, Adetifa I, Taylor S, Bottomley C, Greenwood B, Ota M. Comparison of the prevalence of common bacterial pathogens in the oropharynx and nasopharynx of gambian infants. PLoS One. 2013 Sep 23;8(9):e75558. doi: 10.1371/journal.pone.0075558. eCollection 2013.
citation: Odutola A, Ota MO, Ogundare EO, Antonio M, Owiafe P, Worwui A, Greenwood B, Alderson M, Traskine M, Verlant V, Dobbelaere K, Borys D. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study. Hum Vaccin Immunother. 2016;12(2):393-402. doi: 10.1080/21645515.2015.1111496.
citation: Odutola A, Ota MOC, Antonio M, Ogundare EO, Saidu Y, Foster-Nyarko E, Owiafe PK, Ceesay F, Worwui A, Idoko OT, Owolabi O, Bojang A, Jarju S, Drammeh I, Kampmann B, Greenwood BM, Alderson M, Traskine M, Devos N, Schoonbroodt S, Swinnen K, Verlant V, Dobbelaere K, Borys D. Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study. Vaccine. 2017 May 2;35(19):2531-2542. doi: 10.1016/j.vaccine.2017.03.071. Epub 2017 Apr 4.
citation: Odutola A, Ota MOC, Antonio M, Ogundare EO, Saidu Y, Owiafe PK, Worwui A, Idoko OT, Owolabi O, Kampmann B, Greenwood BM, Alderson M, Traskine M, Swinnen K, Verlant V, Dobbelaere K, Borys D. Immunogenicity of pneumococcal conjugate vaccine formulations containing pneumococcal proteins, and immunogenicity and reactogenicity of co-administered routine vaccines - A phase II, randomised, observer-blind study in Gambian infants. Vaccine. 2019 May 1;37(19):2586-2599. doi: 10.1016/j.vaccine.2019.03.033. Epub 2019 Apr 8.