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Nasopharyngeal Carriage Study in Healthy Kenyan Toddlers

Sponsor
PATH (Other)
Overall Status
Completed
CT.gov ID
NCT02146365
Collaborator
(none)
297
Enrollment
1
Location
16.8
Actual Duration (Months)
17.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluated the change in nasopharyngeal carriage (NPC) of Streptococcus pneumoniae (SPn), hypothesizing that it would be reduced post-vaccination with Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant (PATH-wSP) and that PATH-wSP would remain safe and well-tolerated over the course of the study.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    This study enrolled healthy Kenyan toddlers (12-15 months of age) who participated in the randomized control trial of VAC-010 (NCT02097472), as well as healthy toddlers aged 12 to 15 months who had not participated in the VAC-010 Study. All participants must have received a primary dose of pneumococcal conjugate vaccine (PCV) per local practice prior to enrollment in either VAC-010 or VAC-011. No treatments were administered during this study.

    The study consisted of the following four groups:

    Participants who were randomized in study VAC-010 (2:2:1 ratio), defined according to the treatment received in VAC-010:

      1. PATH-wSP + Booster
      1. PATH-wSP Only
      1. Booster Only
    Participants who did not participate in VAC-010:
      1. No Intervention

    Each group consisted of 2 cohorts of participants, Cohort 1 (300 µg PATH-wSP) and Cohort 2 (600 µg PATH-wSP). Enrollment into Cohorts 1 and 2 occurred sequentially; participants in groups 3 and 4 who did not receive PATH-wSP were also enrolled over time and allocated into one of the two cohorts (300 and 600 µg) in order to control for potential seasonal variation in the NPC of S. pneumoniae.

    Each participant completed a total of 5 scheduled visits. For toddlers enrolled simultaneously in VAC-010, visits corresponded to enrollment (Baseline) and 4, 8, 12, and 24 weeks post final vaccination in VAC-010. For toddlers in the No Intervention group, the first visit corresponded to Baseline and the second to fifth visits corresponded to 12, 16, 20, and 32 weeks later. Nasopharyngeal swabs were taken at each visit following World Health Organization (WHO) guidelines for analysis of nasopharyngeal burden.

    Treatments received during VAC-010 included:

    • PATH-wSP: Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant

    • Synflorix™ booster vaccine: pneumococcal polysaccharide conjugate vaccine (adsorbed)

    • Pentavac booster vaccine: diphtheria, tetanus, pertussis (Whole Cell), hepatitis B (recombinant deoxyribonucleic acid [rDNA]) and Haemophilus influenzae type b conjugate vaccine (adsorbed).

    • Saline control

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    297 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    A Prospective Study to Assess the Nasopharyngeal Carriage of Streptococcus Pneumoniae (SPn), Long Term Safety and Immune Persistence in Healthy Kenyan PCV-Primed Toddlers (12-15 Months of Age) Who Received a Whole Cell Pneumococcal Vaccine (PATH-wSP) Compared to Controls
    Actual Study Start Date :
    Sep 25, 2014
    Actual Primary Completion Date :
    Feb 18, 2016
    Actual Study Completion Date :
    Feb 18, 2016

    Arms and Interventions

    Arm Intervention/Treatment
    PATH-wSP 300 µg + Booster

    Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
    PATH-wSP 300 µg Only

    Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
    PATH-wSP 600 µg + Booster

    Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
    PATH-wSP 600 µg Only

    Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
    Booster Only (300 µg)

    Toddlers who enrolled in Cohort 1 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    Booster Only (600 µg)

    Toddlers who enrolled in Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    No Intervention (300 µg)

    Toddlers who enrolled during Cohort 1 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
    No Intervention (600 µg)

    Toddlers who enrolled during Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).

    Outcome Measures

    Primary Outcome Measures

    1. Prevalence of Streptococcus Pneumoniae in Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional participants enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only plus non-interventional participants enrolled during Cohort 2

    2. Density of Streptococcus Pneumoniae in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number of autolysin (LytA) gene copies detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    Secondary Outcome Measures

    1. Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins [Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).]

      Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)

    2. Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group [Week 32]

      Data reported are the geometric mean concentration at 6 months post-vaccination 2 (Week 32) for each PATH-wSP group divided by the Booster (Synflorix and Pentavax)-only group (N=38). Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid (L460D) and pneumococcal surface protein A family 1 (PspA-Fam1) was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)

    3. Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins [Baseline and Week 32]

      Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA) The fold-change was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG response.

    4. Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2 [Baseline and Week 32]

      The percentage of participants with a seroresponse, defined as a ≥ 2, ≥ 3, and ≥ 4 fold-rise above Baseline in IgG antibody levels against Pneumococcal proteins. Fold-rise was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG level. Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)

    5. Number of Participants With Neutralizing Antibody Response to Pneumolysin [Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)]

      Neutralizing antibody responses to pneumolysin were assessed at Baseline and 6 months post vaccination 2 using an in vitro toxin neutralization assay that measures the ability of antibodies to neutralize wild-type pneumolysin-induced lysis of rabbit red blood cells. Each sample was categorized as negative (< 1/20 dilution) or positive (with titer between 1/20 and 1/320 dilution). Responses at higher dilutions indicate higher levels of neutralizing antibodies to pneumolysin.

    6. Number of Adverse Events (AE) [32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.]

      An AE was defined as any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or psychological/physiologic observations occurring in a person in a clinical study. The AEs collected in this non-interventional study were those that remained open after the last visit in the VAC-010 Study, those attributed to study vaccine in VAC-010 with onset after the participant exited VAC-010, those that were related to a VAC-011 procedure (i.e. blood draw, nasal swab sample), and all serious adverse events.

    7. Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 11A/D/E [11A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    8. Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 13 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    9. Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    10. Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15B/C [15B] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    11. Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    12. Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19F is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    13. Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 3 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    14. Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 35B is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    15. Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 6A/B [6A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    16. Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype NT4b is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    17. Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 11A/D/E [11A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    18. Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 13 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    19. Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 15A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    20. Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 15B/C [15B] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    21. Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 19A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    22. Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 19F in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    23. Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 3 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    24. Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 35B in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    25. Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype 6A/B [6A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    26. Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx [Week 0, Week 12, Week 16, Week 20, Week 32]

      The density of Streptococcus pneumoniae serotype NT4b in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Months to 15 Months
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • For Toddlers Enrolled in VAC-010 (NCT02097472):

    • Randomization in VAC-010.

    • Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.

    • Subject has not completed his or her final vaccination in VAC-010.

    For Toddlers NOT Enrolled in VAC-010 (PCV-primed-only cohort):

    • Healthy Kenyan toddlers between 12 to 15 (inclusive) months of age who have completed their primary Expanded Programme on Immunization (EPI) vaccines, with the exception that the birth dose of oral polio vaccine is not required.

    • Subjects who have not received a PCV booster following primary PCV series.

    • Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.

    • Subjects who were not born premature, had a birth weight of > 2.5 kg, and who have a weight-to-height Z-score of ≥ -2 at the time of enrollment.

    Exclusion Criteria:

    • For Toddlers NOT enrolled in VAC-010 (PCV-primed only):

    • Use of any investigational or non-registered drug within 90 days prior to screening, or planned during the course of study participation.

    • Immunosuppression or immunodeficiency (inclusive of human immunodeficiency virus [HIV]) by medical history (inclusive of possible HIV through maternal fetal transfer at time of birth or through breast milk).

    • Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, by medical history or clinical assessment. This includes abnormal vital signs as assessed by toxicity scoring.

    • Any medical or social condition that in the opinion of the investigator may interfere with the study objectives, pose a risk to the study subject, or prevent the subject from completing the study.

    • An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization (CRO), the investigator or any site personnel.

    • Disorders that required chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to enrollment. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose >10 mg of prednisone (adult dosage) adjusted for equivalent dosing in toddlers by weight. The use of topical glucocorticoids will be permitted.

    • Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study; or anticipation of such administration during the study period.

    • History of meningitis, seizures or any neurological disorder.

    • Subject who has evidence of congenital abnormality or developmental delay.

    • Any evidence of fetal alcohol syndrome or history of alcohol abuse in mother during pregnancy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kenya Medical Research Institute/Walter Reed Project Kisumu Kenya 40100

    Sponsors and Collaborators

    • PATH

    Investigators

    • Principal Investigator: Nekoye Otsyula, MB ChB MSc, Kenya Medical Research Institute/Walter Reed Project

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    PATH
    ClinicalTrials.gov Identifier:
    NCT02146365
    Other Study ID Numbers:
    • VAC-011
    First Posted:
    May 23, 2014
    Last Update Posted:
    Feb 17, 2020
    Last Verified:
    Jan 1, 2020
    Additional relevant MeSH terms:
    Pneumococcal Infections

    Study Results

    Participant Flow

    Recruitment Details This study enrolled healthy Kenyan toddlers who participated in the randomized control trial VAC-010 (NCT02097472) whose parents provided consent to participate in VAC-011. In addition, 50 healthy toddlers who did not participate in the VAC-010 study were enrolled from the community as a pneumococcal conjugate vaccine (PCV)-primed-only open cohort.
    Pre-assignment Detail Participants were enrolled sequentially into Cohort 1 (PATH-wSP 300 µg or control) and Cohort 2 (PATH-wSP 600 µg or control).
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (300 µg) Booster Only (600 µg) No Intervention (300 µg) No Intervention (600 µg)
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later. Toddlers who enrolled during Cohort 1 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix). Toddlers who enrolled during Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
    Period Title: Overall Study
    STARTED 49 49 50 50 24 25 25 25
    COMPLETED 45 45 43 41 22 24 25 24
    NOT COMPLETED 4 4 7 9 2 1 0 1

    Baseline Characteristics

    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention Total
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later. Toddlers who enrolled during Cohort 1 or Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix). Total of all reporting groups
    Overall Participants 49 49 50 50 49 50 297
    Age (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    13.2
    (1.1)
    13.0
    (1.1)
    13.3
    (1.1)
    13.5
    (1.2)
    13.1
    (1.0)
    13.3
    (1.2)
    13.2
    (1.1)
    Sex: Female, Male (Count of Participants)
    Female
    31
    63.3%
    25
    51%
    23
    46%
    24
    48%
    23
    46.9%
    31
    62%
    157
    52.9%
    Male
    18
    36.7%
    24
    49%
    27
    54%
    26
    52%
    26
    53.1%
    19
    38%
    140
    47.1%
    Race/Ethnicity, Customized (Count of Participants)
    Luhya
    3
    6.1%
    1
    2%
    7
    14%
    5
    10%
    2
    4.1%
    1
    2%
    19
    6.4%
    Luo
    45
    91.8%
    47
    95.9%
    43
    86%
    45
    90%
    46
    93.9%
    48
    96%
    274
    92.3%
    Other
    1
    2%
    1
    2%
    0
    0%
    0
    0%
    1
    2%
    1
    2%
    4
    1.3%

    Outcome Measures

    1. Primary Outcome
    Title Prevalence of Streptococcus Pneumoniae in Nasopharynx
    Description The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional participants enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only plus non-interventional participants enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    The Nasopharyngeal Carriage (NPC) population included enrolled participants with at least one post-enrollment swab measurement not associated with a protocol violation that may have interfered with the assessment of NPC outcomes. VAC-010 participants who did not receive both vaccinations were excluded.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 91 47 94 50
    Visit 1 (Week 0)
    76
    155.1%
    43
    87.8%
    86
    172%
    46
    92%
    Visit 2 (Week 12)
    77
    157.1%
    44
    89.8%
    80
    160%
    47
    94%
    Visit 3 (Week 16)
    85
    173.5%
    43
    87.8%
    81
    162%
    45
    90%
    Visit 4 (Week 20)
    85
    173.5%
    43
    87.8%
    81
    162%
    44
    88%
    Visit 5 (Week 32)
    81
    165.3%
    43
    87.8%
    71
    142%
    43
    86%
    2. Primary Outcome
    Title Density of Streptococcus Pneumoniae in the Nasopharynx
    Description The density of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number of autolysin (LytA) gene copies detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    The Nasopharyngeal Carriage (NPC) population with available LytA data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 79 43 85 49
    Visit 1 (Week 0)
    13.5
    12.5
    13.9
    13.8
    Visit 2 (Week 12)
    14.0
    13.0
    16.4
    15.9
    Visit 3 (Week 16)
    14.7
    14.5
    16.8
    16.5
    Visit 4 (Week 20)
    15.1
    14.0
    15.5
    15.1
    Visit 5 (Week 32)
    16.8
    14.9
    14.9
    14.8
    3. Secondary Outcome
    Title Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
    Description Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
    Time Frame Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).

    Outcome Measure Data

    Analysis Population Description
    The Immunogenicity (IG) population includes participants enrolled in Study VAC-010 with at least one usable value in the VAC-011 immunogenicity data set. VAC-010 participants who did not receive both vaccinations were excluded.
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts)
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    Measure Participants 43 40 38 35 38
    Pneumolysoid (L460D): Baseline
    381.12
    330.58
    785.54
    832.32
    497.88
    Pneumolysoid (L460D): 4 weeks post-Vaccination 2
    813.00
    786.26
    1600
    2330.97
    545.42
    Pneumolysoid (L460D): 6 months post-Vaccination 2
    1069.31
    1212.57
    1372.33
    1697.94
    1051.76
    PspA-Fam1 (ELISA): Baseline
    397.94
    382.99
    602.57
    725.31
    513.79
    PspA-Fam1 (ELISA): 4 weeks post-Vaccination 2
    720.33
    571.29
    870.53
    1409.82
    514.81
    PspA-Fam1 (ELISA): 6 months post-Vaccination 2
    873.74
    824.96
    762.72
    1239.01
    796.22
    L460D: Baseline
    261.25
    234.51
    314.86
    346.26
    241.08
    L460D: 4 weeks post-Vaccination 2
    460.91
    440.19
    622.67
    917.86
    303.90
    L460D: 6 months post-Vaccination 2
    499.10
    525.38
    508.30
    701.06
    380.59
    PspA-Fam1 (MSD): Baseline
    172.25
    195.25
    219.55
    231.28
    218.24
    PspA-Fam1 (MSD): 4 weeks post-Vaccination 2
    368.08
    357.83
    349.00
    609.24
    213.82
    PspA-Fam1 (MSD): 6 months post-Vaccination 2
    303.31
    339.07
    362.35
    548.93
    317.09
    PhtD: Baseline
    464.43
    456.19
    464.52
    555.72
    377.18
    PhtD: 4 weeks post-Vaccination 2
    847.28
    773.24
    702.42
    1174.38
    575.56
    PhtD: 6 months post-Vaccination 2
    1128.66
    1163.21
    926.31
    1282.89
    890.03
    BCH0785: Baseline
    401.04
    322.75
    267.80
    371.19
    314.85
    BCH0785: 4 weeks post-Vaccination 2
    555.25
    514.90
    411.22
    761.38
    397.66
    BCH0785: 6 months post-Vaccination 2
    539.24
    602.44
    385.46
    726.43
    460.80
    StkP: Baseline
    193.50
    142.90
    163.30
    246.51
    191.77
    StkP: 4 weeks post-Vaccination 2
    334.14
    240.51
    253.15
    444.83
    235.29
    StkP: 6 months post-Vaccination 2
    304.48
    331.73
    278.27
    470.92
    305.51
    PcpA: Baseline
    320.15
    369.58
    307.97
    464.90
    302.03
    PcpA: 4 weeks post-Vaccination 2
    383.75
    358.39
    387.80
    527.74
    351.00
    PcpA: 6 months post-Vaccination 2
    631.99
    681.06
    633.57
    779.77
    558.79
    SPWCA: Baseline
    676.76
    665.77
    630.23
    669.91
    660.13
    SPWCA: 4 weeks post-Vaccination 2
    852.45
    782.09
    815.92
    965.60
    762.31
    SPWCA: 6 months post-Vaccination 2
    849.99
    908.71
    828.46
    1020.25
    700.71
    PiuA: Baseline
    685.69
    631.45
    585.28
    697.84
    608.91
    PiuA: 4 weeks post-Vaccination 2
    938.09
    867.54
    925.23
    1164.80
    743.11
    PiuA: 6 months post-Vaccination 2
    1035.89
    1274.26
    998.07
    1188.92
    923.97
    PiaA: Baseline
    650.37
    560.35
    604.16
    886.79
    606.15
    PiaA: 4 weeks post-Vaccination 2
    930.90
    851.40
    788.37
    1574.97
    805.26
    PiaA: 6 months post-Vaccination
    1014.92
    1055.71
    732.05
    1428.92
    816.56
    4. Secondary Outcome
    Title Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group
    Description Data reported are the geometric mean concentration at 6 months post-vaccination 2 (Week 32) for each PATH-wSP group divided by the Booster (Synflorix and Pentavax)-only group (N=38). Immunogenicity was evaluated based on the following assays: Immunoglobulin (IgG) response to pneumolysoid (L460D) and pneumococcal surface protein A family 1 (PspA-Fam1) was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
    Time Frame Week 32

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity population
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
    Measure Participants 43 40 38 35
    Pneumolysoid (L460D)
    1.02
    1.15
    1.30
    1.61
    PspA-Fam1 (ELISA)
    1.10
    1.04
    0.96
    1.56
    L460D
    1.31
    1.38
    1.34
    1.84
    PspA-Fam1 (MSD)
    0.96
    1.07
    1.14
    1.73
    PhtD
    1.27
    1.31
    1.04
    1.44
    BCH0785
    1.17
    1.31
    0.84
    1.58
    StkP
    1.00
    1.09
    0.91
    1.54
    PcpA
    1.13
    1.22
    1.13
    1.40
    SPWCA
    1.21
    1.30
    1.18
    1.46
    PiuA
    1.12
    1.38
    1.08
    1.29
    PiaA
    1.24
    1.29
    0.90
    1.75
    5. Secondary Outcome
    Title Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
    Description Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA) The fold-change was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG response.
    Time Frame Baseline and Week 32

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts)
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    Measure Participants 43 40 38 35 38
    Pneumolysoid (L460D)
    2.81
    3.67
    1.75
    2.04
    2.11
    PspA-Fam1 (ELISA)
    2.20
    2.15
    1.27
    1.71
    1.55
    L460D
    1.91
    2.24
    1.61
    2.02
    1.58
    PspA-Fam1 (MSD)
    1.76
    1.74
    1.65
    2.37
    1.45
    PhtD
    2.43
    2.55
    1.99
    2.31
    2.36
    BCH0785
    1.34
    1.87
    1.44
    1.96
    1.59
    StkP
    1.57
    2.32
    1.70
    1.91
    1.59
    PcpA
    1.97
    1.84
    2.06
    1.68
    1.85
    SPWCA
    1.26
    1.36
    1.31
    1.52
    1.06
    PiuA
    1.51
    2.02
    1.71
    1.70
    1.52
    PiaA
    1.56
    1.88
    1.21
    1.61
    1.35
    6. Secondary Outcome
    Title Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2
    Description The percentage of participants with a seroresponse, defined as a ≥ 2, ≥ 3, and ≥ 4 fold-rise above Baseline in IgG antibody levels against Pneumococcal proteins. Fold-rise was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG level. Immunogenicity was evaluated based on the following assays: IgG response to pneumolysoid [L460D] and pneumococcal surface protein A family 1 [PspA-Fam1] was measured by enzyme-linked immunosorbent assay (ELISA). IgG response to the following pneumococcal proteins was measured using the Meso Scale Discovery (MSD) platform: L460D PspA-Fam1 Pneumococcal histidine triad D (PhtD) Boston Children's Hospital protein 785 (BCH0785) Serine threonine kinase protein (StkP) Pneumococcal choline-binding protein A (PcpA) Streptococcus pneumonia whole cell antigen (SPWCA) Pneumococcal iron uptake protein A (PiuA) Pneumococcal iron acquisition protein A (PiaA)
    Time Frame Baseline and Week 32

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts)
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    Measure Participants 43 40 38 35 38
    Pneumolysoid (L460D): ≥ 2 Fold-Rise
    72.1
    147.1%
    87.5
    178.6%
    60.5
    121%
    62.9
    125.8%
    55.3
    112.9%
    Pneumolysoid (L460D): ≥ 3 Fold-Rise
    44.2
    90.2%
    57.5
    117.3%
    28.9
    57.8%
    34.3
    68.6%
    39.5
    80.6%
    Pneumolysoid (L460D): ≥4 Fold-Rise
    44.2
    90.2%
    57.5
    117.3%
    26.3
    52.6%
    34.3
    68.6%
    39.5
    80.6%
    PspA-Fam1 (ELISA): ≥ 2 Fold-Rise
    41.9
    85.5%
    60.0
    122.4%
    28.9
    57.8%
    42.9
    85.8%
    36.8
    75.1%
    PspA-Fam1 (ELISA): ≥ 3 Fold-Rise
    32.6
    66.5%
    42.5
    86.7%
    15.8
    31.6%
    37.1
    74.2%
    26.3
    53.7%
    PspA-Fam1 (ELISA): ≥ 4 Fold-Rise
    25.6
    52.2%
    30.0
    61.2%
    13.2
    26.4%
    22.9
    45.8%
    23.7
    48.4%
    L460D: ≥ 2 Fold-Rise
    46.5
    94.9%
    52.5
    107.1%
    34.2
    68.4%
    48.6
    97.2%
    36.8
    75.1%
    L460D: ≥ 3 Fold-Rise
    23.3
    47.6%
    40.0
    81.6%
    15.8
    31.6%
    31.4
    62.8%
    18.4
    37.6%
    L460D: ≥ 4 Fold-Rise
    14.0
    28.6%
    27.5
    56.1%
    10.5
    21%
    17.1
    34.2%
    10.5
    21.4%
    PspA-Fam1 (MSD): ≥ 2 Fold-Rise
    32.6
    66.5%
    37.5
    76.5%
    44.7
    89.4%
    45.7
    91.4%
    39.5
    80.6%
    PspA-Fam1 (MSD): ≥ 3 Fold-Rise
    25.6
    52.2%
    30.0
    61.2%
    31.6
    63.2%
    42.9
    85.8%
    21.1
    43.1%
    PspA-Fam1 (MSD): ≥ 4 Fold-Rise
    20.9
    42.7%
    27.5
    56.1%
    23.7
    47.4%
    31.4
    62.8%
    15.8
    32.2%
    PhtD: ≥ 2 Fold-Ris2
    58.1
    118.6%
    50.0
    102%
    57.9
    115.8%
    54.3
    108.6%
    60.5
    123.5%
    PhtD: ≥ 3 Fold-Rise
    46.5
    94.9%
    40.0
    81.6%
    28.9
    57.8%
    40.0
    80%
    42.1
    85.9%
    PhtD: ≥ 4 Fold-Rise
    25.6
    52.2%
    35.0
    71.4%
    15.8
    31.6%
    17.1
    34.2%
    28.9
    59%
    BCH0785: ≥ 2 Fold-Rise
    32.6
    66.5%
    50.0
    102%
    42.1
    84.2%
    42.9
    85.8%
    39.5
    80.6%
    BCH0785: ≥ 3 Fold-Rise
    23.3
    47.6%
    27.5
    56.1%
    18.4
    36.8%
    28.6
    57.2%
    26.3
    53.7%
    BCH0785: ≥ 4 Fold-Rise
    14.0
    28.6%
    15.0
    30.6%
    10.5
    21%
    25.7
    51.4%
    15.8
    32.2%
    StkP: ≥ 2 Fold-Rise
    32.6
    66.5%
    52.5
    107.1%
    42.1
    84.2%
    48.06
    96.1%
    36.8
    75.1%
    StkP: ≥ 3 Fold-Rise
    20.9
    42.7%
    32.5
    66.3%
    23.7
    47.4%
    34.3
    68.6%
    21.1
    43.1%
    StkP: ≥ 4 Fold-Rise
    18.6
    38%
    27.5
    56.1%
    10.5
    21%
    20.0
    40%
    13.2
    26.9%
    PcpA: ≥ 2 Fold-Rise
    46.5
    94.9%
    42.5
    86.7%
    50.0
    100%
    40.0
    80%
    39.5
    80.6%
    PcpA: ≥ 3 Fold-Rise
    30.2
    61.6%
    35.0
    71.4%
    34.2
    68.4%
    31.4
    62.8%
    31.6
    64.5%
    PcpA: ≥ 4 Fold-Rise
    25.6
    52.2%
    27.5
    56.1%
    26.3
    52.6%
    22.9
    45.8%
    31.6
    64.5%
    SPWCA: ≥ 2 Fold-Rise
    25.6
    52.2%
    22.5
    45.9%
    26.3
    52.6%
    31.4
    62.8%
    21.1
    43.1%
    SPWCA: ≥ 3 Fold-Rise
    9.3
    19%
    12.5
    25.5%
    10.5
    21%
    2.9
    5.8%
    2.6
    5.3%
    SPWCA: ≥ 4 Fold-Rise
    4.7
    9.6%
    7.5
    15.3%
    0.0
    0%
    0.0
    0%
    2.6
    5.3%
    PiuA: ≥ 2 Fold-Rise
    32.6
    66.5%
    52.5
    107.1%
    39.5
    79%
    45.7
    91.4%
    34.2
    69.8%
    PiuA: ≥ 3 Fold-Rise
    20.9
    42.7%
    27.5
    56.1%
    26.3
    52.6%
    22.9
    45.8%
    13.2
    26.9%
    PiuA: ≥ 4 Fold-Rise
    9.3
    19%
    22.5
    45.9%
    15.8
    31.6%
    17.1
    34.2%
    7.9
    16.1%
    PiaA: ≥ 2 Fold-Rise
    41.9
    85.5%
    40.0
    81.6%
    26.3
    52.6%
    40.0
    80%
    36.8
    75.1%
    PiaA: ≥ 3 Fold-Rise
    23.3
    47.6%
    25.0
    51%
    7.9
    15.8%
    20.0
    40%
    21.1
    43.1%
    PiaA: ≥ 4 Fold-Rise
    11.6
    23.7%
    20.0
    40.8%
    2.6
    5.2%
    17.1
    34.2%
    10.5
    21.4%
    7. Secondary Outcome
    Title Number of Participants With Neutralizing Antibody Response to Pneumolysin
    Description Neutralizing antibody responses to pneumolysin were assessed at Baseline and 6 months post vaccination 2 using an in vitro toxin neutralization assay that measures the ability of antibodies to neutralize wild-type pneumolysin-induced lysis of rabbit red blood cells. Each sample was categorized as negative (< 1/20 dilution) or positive (with titer between 1/20 and 1/320 dilution). Responses at higher dilutions indicate higher levels of neutralizing antibodies to pneumolysin.
    Time Frame Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity Population with available neutralizing antibody data.
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts)
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
    Measure Participants 35 34 37 35 34
    <1:20 titer
    12
    24.5%
    10
    20.4%
    12
    24%
    8
    16%
    17
    34.7%
    1:20 titer
    10
    20.4%
    10
    20.4%
    11
    22%
    8
    16%
    8
    16.3%
    1:40 titer
    8
    16.3%
    8
    16.3%
    9
    18%
    12
    24%
    4
    8.2%
    1:80 titer
    2
    4.1%
    5
    10.2%
    3
    6%
    6
    12%
    4
    8.2%
    1:160 titer
    1
    2%
    0
    0%
    2
    4%
    1
    2%
    1
    2%
    1:320 titer
    2
    4.1%
    1
    2%
    0
    0%
    0
    0%
    0
    0%
    <1:20 titer
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1:20 titer
    11
    22.4%
    12
    24.5%
    11
    22%
    7
    14%
    12
    24.5%
    1:40 titer
    10
    20.4%
    11
    22.4%
    12
    24%
    8
    16%
    12
    24.5%
    1:80 titer
    5
    10.2%
    5
    10.2%
    8
    16%
    10
    20%
    7
    14.3%
    1:160 titer
    7
    14.3%
    5
    10.2%
    4
    8%
    7
    14%
    3
    6.1%
    1:320 titer
    2
    4.1%
    1
    2%
    2
    4%
    3
    6%
    0
    0%
    8. Secondary Outcome
    Title Number of Adverse Events (AE)
    Description An AE was defined as any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or psychological/physiologic observations occurring in a person in a clinical study. The AEs collected in this non-interventional study were those that remained open after the last visit in the VAC-010 Study, those attributed to study vaccine in VAC-010 with onset after the participant exited VAC-010, those that were related to a VAC-011 procedure (i.e. blood draw, nasal swab sample), and all serious adverse events.
    Time Frame 32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later. Toddlers who enrolled during Cohort 1 or Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
    Measure Participants 49 49 50 50 49 50
    Total number of AEs
    0
    0
    1
    4
    1
    1
    Serious AE: No
    0
    0
    1
    0
    0
    0
    Serious AE: Yes
    0
    0
    0
    4
    1
    1
    Severity: Mild (Grade 1)
    0
    0
    1
    0
    0
    1
    Severity: Moderate (Grade 2)
    0
    0
    0
    0
    0
    0
    Severity: Severe (Grade 3)
    0
    0
    0
    4
    1
    1
    Severity: Potentially Life Threatening (Grade 4)
    0
    0
    0
    0
    0
    0
    Severity: Death (Grade 5)
    0
    0
    0
    0
    0
    0
    Related to vaccine: No
    0
    0
    1
    4
    1
    1
    Related to vaccine: Yes
    0
    0
    0
    0
    0
    0
    9. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 11A/D/E [11A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 81 43 83 50
    Visit 1 (Week 0)
    6
    12.2%
    4
    8.2%
    6
    12%
    1
    2%
    Visit 2 (Week 12)
    7
    14.3%
    3
    6.1%
    5
    10%
    1
    2%
    Visit 3 (Week 16)
    2
    4.1%
    4
    8.2%
    7
    14%
    3
    6%
    Visit 4 (Week 20)
    4
    8.2%
    3
    6.1%
    5
    10%
    1
    2%
    Visit 5 (Week 32)
    6
    12.2%
    0
    0%
    9
    18%
    3
    6%
    10. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 13 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    6
    12.2%
    2
    4.1%
    3
    6%
    5
    10%
    Visit 2 (Week 12)
    6
    12.2%
    5
    10.2%
    5
    10%
    3
    6%
    Visit 3 (Week 16)
    4
    8.2%
    3
    6.1%
    5
    10%
    1
    2%
    Visit 4 (Week 20)
    6
    12.2%
    5
    10.2%
    5
    10%
    1
    2%
    Visit 5 (Week 32)
    5
    10.2%
    6
    12.2%
    4
    8%
    2
    4%
    11. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    1
    2%
    0
    0%
    2
    4%
    3
    6%
    Visit 2 (Week 12)
    5
    10.2%
    2
    4.1%
    5
    10%
    4
    8%
    Visit 3 (Week 16)
    8
    16.3%
    1
    2%
    5
    10%
    1
    2%
    Visit 4 (Week 20)
    7
    14.3%
    1
    2%
    6
    12%
    2
    4%
    Visit 5 (Week 32)
    7
    14.3%
    4
    8.2%
    2
    4%
    5
    10%
    12. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15B/C [15B] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    10
    20.4%
    2
    4.1%
    9
    18%
    6
    12%
    Visit 2 (Week 12)
    16
    32.7%
    3
    6.1%
    7
    14%
    5
    10%
    Visit 3 (Week 16)
    9
    18.4%
    4
    8.2%
    5
    10%
    8
    16%
    Visit 4 (Week 20)
    11
    22.4%
    2
    4.1%
    9
    18%
    4
    8%
    Visit 5 (Week 32)
    4
    8.2%
    1
    2%
    4
    8%
    3
    6%
    13. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19A is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    3
    6.1%
    4
    8.2%
    7
    14%
    4
    8%
    Visit 2 (Week 12)
    3
    6.1%
    6
    12.2%
    9
    18%
    5
    10%
    Visit 3 (Week 16)
    1
    2%
    7
    14.3%
    6
    12%
    3
    6%
    Visit 4 (Week 20)
    2
    4.1%
    6
    12.2%
    5
    10%
    6
    12%
    Visit 5 (Week 32)
    7
    14.3%
    3
    6.1%
    3
    6%
    4
    8%
    14. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19F is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    4
    8.2%
    2
    4.1%
    6
    12%
    5
    10%
    Visit 2 (Week 12)
    5
    10.2%
    5
    10.2%
    7
    14%
    3
    6%
    Visit 3 (Week 16)
    4
    8.2%
    5
    10.2%
    10
    20%
    2
    4%
    Visit 4 (Week 20)
    5
    10.2%
    4
    8.2%
    10
    20%
    3
    6%
    Visit 5 (Week 32)
    4
    8.2%
    3
    6.1%
    8
    16%
    2
    4%
    15. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 3 is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    8
    16.3%
    4
    8.2%
    5
    10%
    2
    4%
    Visit 2 (Week 12)
    6
    12.2%
    4
    8.2%
    7
    14%
    1
    2%
    Visit 3 (Week 16)
    9
    18.4%
    4
    8.2%
    11
    22%
    2
    4%
    Visit 4 (Week 20)
    6
    12.2%
    5
    10.2%
    6
    12%
    4
    8%
    Visit 5 (Week 32)
    4
    8.2%
    4
    8.2%
    8
    16%
    1
    2%
    16. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 35B is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    8
    16.3%
    4
    8.2%
    11
    22%
    4
    8%
    Visit 2 (Week 12)
    8
    16.3%
    3
    6.1%
    9
    18%
    4
    8%
    Visit 3 (Week 16)
    5
    10.2%
    6
    12.2%
    8
    16%
    2
    4%
    Visit 4 (Week 20)
    2
    4.1%
    5
    10.2%
    6
    12%
    3
    6%
    Visit 5 (Week 32)
    7
    14.3%
    3
    6.1%
    4
    8%
    1
    2%
    17. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 6A/B [6A] is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    5
    10.2%
    5
    10.2%
    6
    12%
    2
    4%
    Visit 2 (Week 12)
    7
    14.3%
    4
    8.2%
    6
    12%
    3
    6%
    Visit 3 (Week 16)
    5
    10.2%
    6
    12.2%
    7
    14%
    1
    2%
    Visit 4 (Week 20)
    3
    6.1%
    3
    6.1%
    5
    10%
    3
    6%
    Visit 5 (Week 32)
    4
    8.2%
    5
    10.2%
    5
    10%
    2
    4%
    18. Secondary Outcome
    Title Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
    Description Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype NT4b is reported. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    Nasopharyngeal Carriage (NPC) population with culture-confirmed samples and available serotype data at each time point
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 83 43 85 50
    Visit 1 (Week 0)
    29
    59.2%
    17
    34.7%
    27
    54%
    15
    30%
    Visit 2 (Week 12)
    17
    34.7%
    10
    20.4%
    32
    64%
    10
    20%
    Visit 3 (Week 16)
    17
    34.7%
    13
    26.5%
    23
    46%
    10
    20%
    Visit 4 (Week 20)
    12
    24.5%
    15
    30.6%
    26
    52%
    8
    16%
    Visit 5 (Week 32)
    20
    40.8%
    14
    28.6%
    18
    36%
    13
    26%
    19. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 11A/D/E [11A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 7 4 9 3
    Visit 1 (Week 0)
    11.9
    15.0
    12.9
    14
    Visit 2 (Week 12)
    10.9
    17.6
    14.4
    18.5
    Visit 3 (Week 16)
    9.8
    13.6
    16.6
    14.1
    Visit 4 (Week 20)
    15.1
    12.3
    15.8
    5.4
    Visit 5 (Week 32)
    16.3
    14.5
    16.4
    20. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 13 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 6 6 5 5
    Visit 1 (Week 0)
    12.9
    17.1
    12.2
    12.3
    Visit 2 (Week 12)
    10.6
    11.6
    15.0
    12.1
    Visit 3 (Week 16)
    14.2
    15.6
    17.7
    13.8
    Visit 4 (Week 20)
    13.2
    13.1
    13.4
    14.6
    Visit 5 (Week 32)
    14.5
    14.7
    15.8
    16.2
    21. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 15A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 8 4 6 5
    Visit 1 (Week 0)
    13.7
    16.1
    11.0
    Visit 2 (Week 12)
    14.1
    13.8
    18.5
    16.3
    Visit 3 (Week 16)
    14.1
    12.3
    15.8
    18.9
    Visit 4 (Week 20)
    13.7
    13.1
    13.7
    15.8
    Visit 5 (Week 32)
    18.0
    16.3
    15.2
    12.9
    22. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 15B/C [15B] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 16 4 9 8
    Visit 1 (Week 0)
    13.2
    10.3
    12.1
    14.7
    Visit 2 (Week 12)
    13.0
    10.4
    15.8
    17.9
    Visit 3 (Week 16)
    13.7
    13.5
    20.0
    17.3
    Visit 4 (Week 20)
    13.9
    17.5
    14.9
    17.2
    Visit 5 (Week 32)
    16.7
    17.3
    11.2
    12.8
    23. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 19A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 7 7 9 6
    Visit 1 (Week 0)
    10.3
    12.9
    12.3
    11.0
    Visit 2 (Week 12)
    14.2
    12.3
    16.9
    15.5
    Visit 3 (Week 16)
    15.1
    10.6
    16.7
    14.6
    Visit 4 (Week 20)
    18.1
    15.3
    13.3
    14.9
    Visit 5 (Week 32)
    17.0
    15.2
    12.2
    12.9
    24. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 19F in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 5 5 10 5
    Visit 1 (Week 0)
    14.6
    12.2
    12.7
    12.9
    Visit 2 (Week 12)
    13.3
    13.7
    12.2
    18.2
    Visit 3 (Week 16)
    14.6
    13.0
    16.1
    9.9
    Visit 4 (Week 20)
    12.8
    14.9
    16.7
    11.1
    Visit 5 (Week 32)
    14.6
    17.7
    15.3
    14.1
    25. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 3 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 9 5 11 4
    Visit 1 (Week 0)
    12.7
    11.1
    9.7
    12.4
    Visit 2 (Week 12)
    14.2
    11.0
    16.4
    13.3
    Visit 3 (Week 16)
    13.9
    12.7
    15.2
    15.4
    Visit 4 (Week 20)
    13.3
    14.1
    14.7
    17.9
    Visit 5 (Week 32)
    14.6
    14.2
    13.6
    16.6
    26. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 35B in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 8 6 11 4
    Visit 1 (Week 0)
    14.1
    11.1
    13.1
    12.3
    Visit 2 (Week 12)
    14.3
    9.1
    14.0
    14.3
    Visit 3 (Week 16)
    13.8
    15.5
    15.3
    19.3
    Visit 4 (Week 20)
    8.6
    16.8
    12.8
    11.7
    Visit 5 (Week 32)
    16.0
    13.4
    14.5
    12.2
    27. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype 6A/B [6A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 7 6 7 3
    Visit 1 (Week 0)
    14.5
    12.4
    13.4
    11.6
    Visit 2 (Week 12)
    15.0
    12.6
    14.7
    15.8
    Visit 3 (Week 16)
    14.6
    15.0
    14.9
    14.8
    Visit 4 (Week 20)
    20.5
    11.7
    16.6
    12.7
    Visit 5 (Week 32)
    17.2
    14.9
    14.5
    12.6
    28. Secondary Outcome
    Title Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
    Description The density of Streptococcus pneumoniae serotype NT4b in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups: PATH-wSP 300 µg: Combines groups who received 300 µg PATH-wSP with or without booster Control (300 µg): Participants in VAC-010 Cohort 1 who received booster-only, plus non-interventional group enrolled during Cohort 1 PATH-wSP 600 µg: Combines groups who received 600 µg PATH-wSP with or without booster Control (600 µg): Participants in VAC-010 Cohort 2 who received booster-only, plus non-interventional group enrolled during Cohort 2
    Time Frame Week 0, Week 12, Week 16, Week 20, Week 32

    Outcome Measure Data

    Analysis Population Description
    NPC population with culture-confirmed samples and a relative abundance greater than zero for the serotype.
    Arm/Group Title Combined PATH-wSP 300 µg Combined Control (300 µg) Combined PATH-wSP 600 µg Combined Control (600 µg)
    Arm/Group Description All participants who received PATH-wSP 300 µg, including participants in the PATH-wSP 300 µg + Booster and participants in the PATH-wSP 300 µg Only treatment groups. Participants enrolled during Cohort 1 who received booster-only or no intervention. All participants who received PATH-wSP 600 µg, including participants in the PATH-wSP 600 µg + Booster and participants in the PATH-wSP 600 µg Only treatment groups. All participants enrolled during Cohort 2 who received booster-only or no intervention.
    Measure Participants 29 17 32 15
    Visit 1 (Week 0)
    11.7
    9.8
    10.7
    11.7
    Visit 2 (Week 12)
    12.1
    12.2
    13.4
    12.1
    Visit 3 (Week 16)
    11.7
    12.1
    13.7
    13.7
    Visit 4 (Week 20)
    12.4
    9.6
    12.1
    11.5
    Visit 5 (Week 32)
    14.2
    11.7
    12.1
    12.2

    Adverse Events

    Time Frame 32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.
    Adverse Event Reporting Description The AEs collected in this non-interventional study were those that remained open after the last visit in the VAC-010 Study, those attributed to study vaccine in VAC-010 with onset after the participant exited VAC-010, those that were related to a VAC-011 procedure (i.e. blood draw, nasal swab sample), and all serious adverse events.
    Arm/Group Title PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention
    Arm/Group Description Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later. Toddlers who enrolled in Cohort 1 or Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later. Toddlers who enrolled during Cohort 1 or Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
    All Cause Mortality
    PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/49 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%)
    Serious Adverse Events
    PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/49 (0%) 0/49 (0%) 0/50 (0%) 3/50 (6%) 1/49 (2%) 1/50 (2%)
    Infections and infestations
    Cerebral malaria 0/49 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%)
    Urinary tract infection 0/49 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%)
    Pneumonia 0/49 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%)
    Malaria 0/49 (0%) 0/49 (0%) 0/50 (0%) 1/50 (2%) 1/49 (2%) 1/50 (2%)
    Other (Not Including Serious) Adverse Events
    PATH-wSP 300 µg + Booster PATH-wSP 300 µg Only PATH-wSP 600 µg + Booster PATH-wSP 600 µg Only Booster Only (Both Cohorts) No Intervention
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/49 (0%) 0/49 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%)
    Metabolism and nutrition disorders
    Malnutrition 0/49 (0%) 0/49 (0%) 1/50 (2%) 0/50 (0%) 0/49 (0%) 0/50 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jorge Flores
    Organization PATH
    Phone (202) 822-0033
    Email jeflores@path.org
    Responsible Party:
    PATH
    ClinicalTrials.gov Identifier:
    NCT02146365
    Other Study ID Numbers:
    • VAC-011
    First Posted:
    May 23, 2014
    Last Update Posted:
    Feb 17, 2020
    Last Verified:
    Jan 1, 2020