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CompletedNCT01204658Updated May 29, 2019Results posted

Safety & Immunogenicity of Pneumococcal Vaccine 2189242A Co-administered With DTPa-HBV-IPV/Hib in Healthy Infants

A Phase 2 interventional study of Pneumococcal vaccine GSK 2189242A (LD formulation 1) and Pneumococcal vaccine GSK 2189242A (HD formulation 2) in Infections, Streptococcal, sponsored by GlaxoSmithKline. Completed at 24 sites in 4 countries. Open to participants aged 6 Weeks to 14 Weeks, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-05-29.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
576
Allocation
Randomized
Ages
6 Weeks to 14 Weeks
Sex
All
01

Study summary

This study will assess the safety, reactogenicity and immunogenicity of two formulations of GSK Biologicals' pneumococcal vaccine 2189242A given as a 3-dose primary vaccination course during the first 6 months of life followed by a booster dose at 12-15 months of age and co-administered with DTPa-HBV-IPV/Hib vaccine.

Read the detailed description

This study will assess the safety, reactogenicity, immunogenicity and persistence of two formulations of GSK Biologicals' pneumococcal vaccine 2189242A [high dose (HD) or low dose (LD)] given as a 3-dose primary vaccination course during the first 6 months of life followed by a booster dose at 12-15 months of age when co-administered with Infanrix hexa™ and compared to the vaccination with Synflorix™ and with Prevnar 13™ similarly co-administered with the Infanrix hexa™ vaccine.

02

Conditions studied

  • Infections, Streptococcal

Keywords

  • Haemophilus influenzae
  • Streptococcus pneumoniae
  • immunogenicity
  • Pneumococcal vaccine
  • infants
  • safety
03

In context

Streptococcal Infections

155 studies on the registry are indexed under Streptococcal Infections; 15 are open to participants now.

This study's enrollment of 576 is above the median of 250 across 105 interventional studies indexed under Streptococcal Infections.

Browse Streptococcal Infections studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Weeks to 14 Weeks
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol
  • Male or female between, and including, 6 and 14 weeks (42-104 days) of age at the time of the first vaccination.
  • Written informed consent obtained from the parents/LAR(s) of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Born after a gestation period of 36 to 42 weeks inclusive.

Exclusion criteria

Exclusion Criteria:

  • Child in care.
  • Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
  • Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the exception of licensed flu vaccines.
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
  • Previous vaccination against S. pneumoniae since birth.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects or any chronic illness.
  • History of any neurologic disorders or seizures.
  • Acute disease and/or fever at the time of enrolment.
  • Fever is defined as temperature >= 38.0°C on rectal setting or >= 37.5°C on oral or axillary setting.
  • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  • Administration of immunoglobulins and/ or any blood products since birth or planned administration during the primary epoch and during the period starting three months before booster vaccination and ending one month after the booster vaccination.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
576 participants (actual)

Study arms

  • Experimental
    10PP-LD/Infanrix hexa Group

    This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with low doses (LD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD) co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of the 10PP and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for the 10PP vaccine and on the right side for Infanrix hexa™.

    Biological: Pneumococcal vaccine GSK 2189242A (LD formulation 1) · Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

  • Experimental
    10PP-HD/Infanrix hexa Group

    This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with high doses (HD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD), co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of the 10PP and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for the 10PP vaccine and on the right side for Infanrix hexa™.

    Biological: Pneumococcal vaccine GSK 2189242A (HD formulation 2) · Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

  • Active comparator
    Synflorix/Infanrix hexa Group

    This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Synflorix™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of Synflorix™ and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for Synflorix™ and on the right side for Infanrix hexa™.

    Biological: Synflorix · Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

  • Active comparator
    Prevnar 13/Infanrix hexa Group

    This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Prevnar 13™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10. The 3 primary doses of Prevnar 13™ and Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the right and left side, respectively. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for Prevnar 13™ and on the right side for Infanrix hexa™.

    Biological: Prevenar 13 · Biological: Infanrix Hexa (DTPa-HBV-IPV/Hib)

Interventions

  • BiologicalPneumococcal vaccine GSK 2189242A (LD formulation 1)

    Intramuscular injection

    Also known as: GSK 2189242A; 10PP-LD

  • BiologicalPneumococcal vaccine GSK 2189242A (HD formulation 2)

    Intramuscular injection

    Also known as: GSK 2189242A; 10PP-HD

  • BiologicalSynflorix

    Intramuscular injection

  • BiologicalPrevenar 13

    Intramuscular injection

  • BiologicalInfanrix Hexa (DTPa-HBV-IPV/Hib)

    Intramuscular injection

06

What researchers measure

Primary outcomes

  1. Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study

    Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than or equal to \[\>=\] 38 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 (G3) Drowsiness = Drowsiness that prevented normal activity. G3 Irritability = Crying that could not be comforted/prevented normal activity. G3 Loss of appetite = Subject did not eat at all. G3 Fever = Rectal temperature higher than (\>) 40.0°C. Primary results correspond to results for occurrences of G3 fever symptoms assessed by the investigators as related to vaccination (Related G3 fever).

    Time frame: Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course

  2. Percentage of Subjects Reporting Fever > 40.0°C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in 10PP-LD/Infanrix Hexa Group and in Synflorix/Infanrix Hexa Group

    Grade 3 fever was defined as fever by rectal measurement \> 40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-LD/Infanrix hexa (or 10PP-LD) and Synflorix/Infanrix hexa (or 10PN) groups only.

    Time frame: During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

  3. Percentage of Subjects Reporting Fever > 40° C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in the 10PP-HD/Infanrix Hexa Group and in the Synflorix/Infanrix Hexa Group

    Grade 3 fever was defined as fever by rectal measurement \>40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-HD/Infanrix hexa (or 10PP-HD) and Synflorix/Infanrix hexa (or 10PN) groups only.

    Time frame: During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

Secondary outcomes

  1. Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Primary Phase of the Study

    Antibody concentrations against dPly and PhtD (anti-dPly and anti-PhtD, respectively) were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). Cut-offs for seropositivity were concentrations higher than or equal to (≥)12 EL.U/mL for anti-dPly antibodies and ≥ 17 EL.U/mL for anti-PhtD antibodies. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  2. Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Booster Phase of the Study

    Antibody concentrations against dPly and PhtD (anti-dPly and anti-PhtD, respectively) were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). Cut-offs for seropositivity were concentrations higher than or equal to (≥)12 EL.U/mL for anti-dPly antibodies and ≥ 17 EL.U/mL for anti-PhtD antibodies. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  3. Antibody Concentrations Against Protein D (Anti-PD) - Primary Phase of the Study

    Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was a concentration of anti-PD antibodies ≥ 100 EL.U/mL. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  4. Antibody Concentrations Against Protein D (Anti-PD) - Booster Phase of the Study

    Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was a concentration of anti-PD antibodies ≥ 100 EL.U/mL. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  5. Antibody Concentrations Against Pneumococcal Serotypes - Primary Phase of the Study

    Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  6. Antibody Concentrations Against Pneumococcal Serotypes - Booster Phase of the Study

    Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  7. Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes - Primary Phase of the Study

    Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The Seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  8. Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes - Booster Phase of the Study

    Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The Seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  9. Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid Haemolysis Activity - Primary Phase of the Study

    Analysis of the concentrations of antibodies inhibiting pneumococcal pneumolysin toxoid haemolysis activity (anti-Ply) was not performed as no assay was validated to perform this analysis. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  10. Concentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid Haemolysis Activity - Booster Phase of the Study

    Analysis of the concentrations of antibodies inhibiting pneumococcal pneumolysin toxoid haemolysis activity (anti-Ply) was not performed as no assay was validated to perform this analysis. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  11. Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Primary Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.1 IU/mL. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  12. Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Booster Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.1 IU/mL. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  13. Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Primary Phase of the Study

    Antibody concentrations will be measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs) in Elisa Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 5 EL.U/mL. This outcome concerns results for the primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  14. Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Booster Phase of the Study

    Antibody concentrations will be measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs) in Elisa Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 5 EL.U/mL. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  15. Concentrations of Antibodies Against Hepatitis B (Anti-HBs) - Primary Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Primary Phase of the study. Note that the percentage of subjects with concentration ≥10 mIU/mL was over-estimated due to the use of in-house assay overestimating concentrations between 10-100 mIU/mL. Accordingly GMCs were also overestimated.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  16. Concentrations of Antibodies Against Hepatitis B (Anti-HBs) - Booster Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Booster Phase of the study. \* A decrease in the specificity of the anti-HB Enzyme-Linked ImmunoSorbent Assay (ELISA) assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete reanalysis. The retest has been performed in using Food and Drug Administration (FDA)-approved ChemiLuminescence ImmunoAssay (CLIA) commercial assay Centaur™.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  17. Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Primary Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.15 µg/mL or 1 µg/mL. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  18. Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Booster Phase of the Study

    Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.15 µg/mL or 1 µg/mL. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  19. Titers of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Primary Phase of the Study

    Antibody titers will be measured by virus microneutralization test, expressed as geometric mean titers (GMTs). The cut-off of the assay for anti-1, anti-2 and anti-3 antibody was a titer higher than or equal to (≥) 8. This outcome concerns results for the Primary Phase of the study.

    Time frame: At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  20. Titers of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Booster Phase of the Study

    Antibody titers will be measured by virus microneutralization test, expressed as geometric mean titers (GMTs). The cut-off of the assay for anti-1, anti-2 and anti-3 antibody was a titer higher than or equal to (≥) 8. This outcome concerns results for the Booster Phase of the study.

    Time frame: At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

  21. Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Primary Phase of the Study

    Assessed local symptoms were pain, redness and swelling at injection site. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (\>) 30 millimeters (mm).

    Time frame: Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course

  22. Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Booster Phase of the Study

    Assessed local symptoms were pain, redness and swelling at injection site. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (\>) 30 millimeters (mm).

    Time frame: Within the 7-day (Days 0-6) period after booster vaccination

  23. Number of Subjects With Any, Grade 3 Solicited General Symptoms and Solicited General Symptoms With Relationship to Vaccination - Booster Phase of the Study

    Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than \[≥\] 38 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigator as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Axillary temperature higher than (\>) 40.0°C.

    Time frame: Within the 7-day (Days 0-6) period post vaccination after booster vaccination

  24. Number of Subjects With Unsolicited Adverse Events (AEs) - Primary Phase of the Study

    An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

    Time frame: Within the 31-day (Days 0-30) period post primary vaccination, across doses

  25. Number of Subjects With Unsolicited Adverse Events (AEs) - Booster Phase of the Study

    An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

    Time frame: Within the 31-day (Days 0-30) period post booster vaccination

  26. Number of Subjects With Serious Adverse Events (SAEs)

    An SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of an SAE, regardless of relationship to vaccination.

    Time frame: During the entire study period (Months 0-11)

07

Results

Posted Sep 28, 2016

Participant flow

A total of 576 subjects were initially enrolled in the study. Of these, one subject was older than protocol defined age range for the first vaccination, and therefore did not receive any vaccination.

Primary Phase
Participant flow — Primary Phase
Milestone10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Started146142145142
Completed146142144142
Not completed0010
Withdrew: Adverse event0010
Booster Phase
Participant flow — Booster Phase
Milestone10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Started144140140140
Completed144140140140
Not completed0000

Outcome measures

PrimaryNumber of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study

Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than or equal to \[\>=\] 38 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 (G3) Drowsiness = Drowsiness that prevented normal activity. G3 Irritability = Crying that could not be comforted/prevented normal activity. G3 Loss of appetite = Subject did not eat at all. G3 Fever = Rectal temperature higher than (\>) 40.0°C. Primary results correspond to results for occurrences of G3 fever symptoms assessed by the investigators as related to vaccination (Related G3 fever).

Time frame:
Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course
Reported as:
Count of participants · Participants
Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Any Drowsiness, post D182767277
G3 Drowsiness, post D14022
Related Drowsiness, post D163585258
Any Irritability, post D193828982
G3 Irritability, post D16995
Related Irritability, post D170626657
Any Loss Appet., post D138323932
G3 Loss Appet., post D10100
Related Loss Appet., post D128262921
Any Fever, post D145325328
G3 Fever, post D10000
Related Fever, post D133254427
Related G3 Fever, post D10000
Any Drowsiness, post D271637066
G3 Drowsiness, post D24211
Related Drowsiness, post D253495655
Any Irritability, post D288818687
G3 Irritability, post D28356
Related Irritability, post D269666667
Any Loss Appet., post D232302830
G3 Loss Appet., post D21200
Related Loss Appet., post D223211825
Any Fever, post D240503838
G3 Fever, post D20000
Related Fever, post D232393331
Related G3 Fever, post D20000
Any Drowsiness, post D357485648
Grade 3 Drowsiness, post D32011
Related Drowsiness, post D351384436
Any Irritability, post D362736272
G3 Irritability, post D37132
Related Irritability, post D352554853
Any Loss Appet., post D328252421
G3 Loss Appet., post D30022
Related Loss Appet., post D322201813
Any Fever, post D328232730
G3 Fever, post D30000
Related Fever, post D323192022
Related G3 Fever, post D30000
PrimaryPercentage of Subjects Reporting Fever > 40.0°C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in 10PP-LD/Infanrix Hexa Group and in Synflorix/Infanrix Hexa Group

Grade 3 fever was defined as fever by rectal measurement \> 40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-LD/Infanrix hexa (or 10PP-LD) and Synflorix/Infanrix hexa (or 10PN) groups only.

Time frame:
During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses
Reported as:
Number · Percentage of participants
Percentage of Subjects Reporting Fever > 40.0°C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in 10PP-LD/Infanrix Hexa Group and in Synflorix/Infanrix Hexa Group
Percentage of participants10PP-LD/Infanrix Hexa GroupSynflorix/Infanrix Hexa Group
Fever>40.0°C & Related Dose 10.00.0
Fever>40.0°C & Related Dose 20.00.0
Fever>40.0°C & Related Dose 30.00.0
Fever>40.0°C & Related across doses0.00.0
Statistical analysis
  • 10PP-LD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.57
  • 10PP-LD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.57
  • 10PP-LD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.62 to 2.57
  • 10PP-LD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.57
PrimaryPercentage of Subjects Reporting Fever > 40° C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in the 10PP-HD/Infanrix Hexa Group and in the Synflorix/Infanrix Hexa Group

Grade 3 fever was defined as fever by rectal measurement \>40.0°C. Related was defined as causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-HD/Infanrix hexa (or 10PP-HD) and Synflorix/Infanrix hexa (or 10PN) groups only.

Time frame:
During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses
Reported as:
Number · Percentage of participants
Percentage of Subjects Reporting Fever > 40° C With Causal Relationship to Vaccination After Each Primary Vaccination Dose and Across Doses in the 10PP-HD/Infanrix Hexa Group and in the Synflorix/Infanrix Hexa Group
Percentage of participants10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa Group
Fever>40.0°C & Related Dose 10.00.0
Fever>40.0°C & Related Dose 20.00.0
Fever>40.0°C & Related Dose 30.00.0
Fever>40.0°C & Related across doses0.00.0
Statistical analysis
  • 10PP-HD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.64
  • 10PP-HD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.64
  • 10PP-HD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.63 to 2.66
  • 10PP-HD/Infanrix Hexa Group vs Synflorix/Infanrix Hexa Group · Kem Phillip's statistical test · p = 0.003 (1-sided P-value computed using Kem Philips' approach for ruling out an increase in % subjects with fever \> 40.0°C and causal relationship to vaccination \> the boundary expressed as 5% + 0.5\*rate in the Synflorix group.) · Difference in percentage: 0 · 95% CI -2.61 to 2.64
SecondaryAntibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Primary Phase of the Study

Antibody concentrations against dPly and PhtD (anti-dPly and anti-PhtD, respectively) were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). Cut-offs for seropositivity were concentrations higher than or equal to (≥)12 EL.U/mL for anti-dPly antibodies and ≥ 17 EL.U/mL for anti-PhtD antibodies. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Primary Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Anti-dPly - At Month 39408.42 (8182.15 to 10818.47)12137.96 (10641.83 to 13844.44)459.97 (398.31 to 531.18)472.88 (404.48 to 552.86)
Anti-PhtD - At Month 31456.57 (1250.65 to 1696.39)1996.61 (1734.17 to 2298.75)523.61 (453.71 to 604.28)552.01 (469.55 to 648.95)
SecondaryAntibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Booster Phase of the Study

Antibody concentrations against dPly and PhtD (anti-dPly and anti-PhtD, respectively) were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). Cut-offs for seropositivity were concentrations higher than or equal to (≥)12 EL.U/mL for anti-dPly antibodies and ≥ 17 EL.U/mL for anti-PhtD antibodies. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Antibody Concentrations Against Pneumococcal Pneumolysin Toxoid (dPly) and Pneumococcal Histidine Triad Protein D (PhtD) Proteins - Booster Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Anti-dPly - Month 106674.42 (5628.57 to 7914.60)5592.85 (4750.83 to 6584.10)495.02 (393.19 to 623.22)737.71 (587.67 to 926.06)
Anti-dPly - Month 1124720.40 (21863.04 to 27951.19)29838.18 (26892.53 to 33106.48)582.85 (463.40 to 733.09)791.42 (628.23 to 997.00)
Anti-PhtD - Month 10910.80 (718.85 to 1154.00)829.12 (671.12 to 1024.32)209.27 (153.16 to 285.95)381.66 (274.64 to 530.39)
Anti-PhtD - Month 113528.25 (2952.68 to 4216.01)3777.39 (3181.74 to 4484.55)266.58 (190.06 to 373.91)469.16 (335.29 to 656.46)
SecondaryAntibody Concentrations Against Protein D (Anti-PD) - Primary Phase of the Study

Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was a concentration of anti-PD antibodies ≥ 100 EL.U/mL. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Antibody Concentrations Against Protein D (Anti-PD) - Primary Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Antibody Concentrations Against Protein D (Anti-PD) - Primary Phase of the Study1135.7 (927.8 to 1390.1)1323.3 (1099.7 to 1592.4)1539.0 (1258.4 to 1882.1)147.0 (112.3 to 192.3)
SecondaryAntibody Concentrations Against Protein D (Anti-PD) - Booster Phase of the Study

Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was a concentration of anti-PD antibodies ≥ 100 EL.U/mL. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Antibody Concentrations Against Protein D (Anti-PD) - Booster Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Anti-PD - Month 10434.3 (365.5 to 516.0)472.8 (403.1 to 554.5)698.2 (593.7 to 821.0)81.0 (69.8 to 93.9)
Anti-PD - Month 111655.4 (1398.2 to 1960.0)1631.0 (1404.5 to 1894.2)2394.2 (2045.7 to 2802.1)85.7 (73.6 to 99.8)
SecondaryAntibody Concentrations Against Pneumococcal Serotypes - Primary Phase of the Study

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · µg/mL
Antibody Concentrations Against Pneumococcal Serotypes - Primary Phase of the Study
µg/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-1 At Month 31.57 (1.36 to 1.80)1.58 (1.36 to 1.83)1.49 (1.28 to 1.74)2.20 (1.86 to 2.60)
ANTI-4 At Month 32.04 (1.74 to 2.39)2.11 (1.83 to 2.43)1.82 (1.55 to 2.14)2.43 (2.05 to 2.88)
ANTI-5 At Month 32.46 (2.13 to 2.85)2.55 (2.22 to 2.92)2.31 (2.00 to 2.67)2.77 (2.27 to 3.38)
ANTI-6B At Month 30.36 (0.29 to 0.46)0.37 (0.31 to 0.45)0.40 (0.32 to 0.51)0.46 (0.37 to 0.57)
ANTI-7F At Month 32.12 (1.86 to 2.41)2.21 (1.97 to 2.48)2.20 (1.92 to 2.50)2.94 (2.51 to 3.46)
ANTI-9V At Month 31.83 (1.59 to 2.12)1.95 (1.73 to 2.20)1.99 (1.72 to 2.30)2.33 (1.96 to 2.76)
ANTI-14 At Month 33.57 (3.08 to 4.14)3.72 (3.30 to 4.18)3.91 (3.41 to 4.48)4.18 (3.41 to 5.13)
ANTI-18C At Month 32.27 (1.93 to 2.67)2.18 (1.84 to 2.59)2.45 (2.04 to 2.95)2.56 (2.14 to 3.07)
ANTI-19F At Month 34.29 (3.63 to 5.07)4.13 (3.52 to 4.85)4.51 (3.79 to 5.36)3.50 (2.94 to 4.18)
ANTI-23F At Month 30.67 (0.54 to 0.82)0.62 (0.50 to 0.78)0.67 (0.54 to 0.82)1.48 (1.17 to 1.88)
ANTI-3 (At Month 30.05 (0.04 to 0.06)0.06 (0.05 to 0.07)0.05 (0.05 to 0.06)2.47 (2.08 to 2.93)
ANTI-6A At Month 30.13 (0.10 to 0.16)0.11 (0.09 to 0.14)0.11 (0.09 to 0.14)2.05 (1.69 to 2.50)
ANTI-19A At Month 30.18 (0.14 to 0.23)0.17 (0.13 to 0.21)0.16 (0.13 to 0.20)2.77 (2.34 to 3.28)
SecondaryAntibody Concentrations Against Pneumococcal Serotypes - Booster Phase of the Study

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · µg/mL
Antibody Concentrations Against Pneumococcal Serotypes - Booster Phase of the Study
µg/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-1 Month 100.30 (0.25 to 0.35)0.30 (0.26 to 0.36)0.26 (0.22 to 0.31)0.49 (0.43 to 0.55)
ANTI-1 Month 112.62 (2.27 to 3.04)2.61 (2.27 to 3.00)2.41 (2.06 to 2.82)3.78 (3.34 to 4.28)
ANTI-4 Month 100.50 (0.43 to 0.58)0.51 (0.43 to 0.61)0.58 (0.49 to 0.70)0.40 (0.35 to 0.46)
ANTI-4 Month 114.10 (3.54 to 4.74)3.90 (3.35 to 4.53)3.98 (3.51 to 4.52)4.36 (3.77 to 5.05)
ANTI-5 Month 100.59 (0.50 to 0.69)0.58 (0.49 to 0.68)0.55 (0.47 to 0.65)0.85 (0.74 to 0.99)
ANTI-5 Month 113.48 (2.98 to 4.05)3.44 (2.98 to 3.96)3.33 (2.87 to 3.87)7.52 (6.52 to 8.68)
ANTI-6B Month 100.45 (0.38 to 0.53)0.47 (0.39 to 0.56)0.46 (0.38 to 0.55)0.25 (0.21 to 0.31)
ANTI-6B Month 112.04 (1.77 to 2.36)1.96 (1.67 to 2.30)2.28 (1.94 to 2.68)3.11 (2.65 to 3.64)
ANTI-7F Month 100.94 (0.82 to 1.09)1.00 (0.88 to 1.15)0.98 (0.85 to 1.13)1.34 (1.18 to 1.53)
ANTI-7F Month 114.72 (4.13 to 5.40)4.70 (4.19 to 5.27)4.87 (4.32 to 5.50)7.68 (6.84 to 8.61)
ANTI-9V Month 100.77 (0.65 to 0.90)0.97 (0.84 to 1.12)0.99 (0.85 to 1.16)0.58 (0.50 to 0.68)
ANTI-9V Month 114.48 (3.90 to 5.14)4.91 (4.32 to 5.58)5.20 (4.52 to 5.97)6.57 (5.67 to 7.60)
ANTI-14 Month 101.36 (1.12 to 1.65)1.43 (1.18 to 1.73)1.57 (1.28 to 1.93)2.06 (1.72 to 2.47)
ANTI-14 Month 116.06 (5.18 to 7.09)7.18 (6.14 to 8.39)6.63 (5.59 to 7.86)11.43 (9.81 to 13.30)
ANTI-18C Month 100.75 (0.64 to 0.87)0.76 (0.65 to 0.89)0.92 (0.77 to 1.10)0.75 (0.65 to 0.85)
ANTI-18C Month 116.68 (5.76 to 7.75)6.38 (5.48 to 7.42)7.65 (6.76 to 8.67)6.40 (5.50 to 7.45)
ANTI-19F Month 101.25 (1.05 to 1.47)1.13 (0.96 to 1.33)1.30 (1.06 to 1.58)0.66 (0.53 to 0.82)
ANTI-19F Month 116.73 (5.77 to 7.83)7.22 (6.25 to 8.33)7.84 (6.78 to 9.06)7.43 (6.35 to 8.69)
ANTI-23F Month 100.46 (0.38 to 0.56)0.47 (0.38 to 0.58)0.57 (0.48 to 0.68)0.37 (0.30 to 0.44)
ANTI-23F Month 113.20 (2.68 to 3.83)3.20 (2.70 to 3.78)3.72 (3.21 to 4.31)7.10 (6.05 to 8.35)
ANTI-3 Month 100.05 (0.04 to 0.06)0.05 (0.04 to 0.06)0.05 (0.04 to 0.06)0.32 (0.27 to 0.38)
ANTI-3 Month 110.06 (0.05 to 0.08)0.05 (0.04 to 0.07)0.06 (0.05 to 0.07)1.83 (1.58 to 2.12)
ANTI-6A Month 100.19 (0.15 to 0.24)0.18 (0.15 to 0.22)0.20 (0.16 to 0.24)0.70 (0.59 to 0.83)
ANTI-6A Month 110.89 (0.72 to 1.11)0.74 (0.59 to 0.93)0.99 (0.78 to 1.26)7.77 (6.60 to 9.14)
ANTI-19A Month 100.18 (0.15 to 0.22)0.15 (0.12 to 0.18)0.18 (0.14 to 0.22)0.57 (0.44 to 0.73)
ANTI-19A Month 111.12 (0.89 to 1.41)1.03 (0.80 to 1.31)1.23 (0.99 to 1.52)7.77 (6.43 to 9.39)
SecondaryTiters for Opsonophagocytic Activity Against Pneumococcal Serotypes - Primary Phase of the Study

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The Seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · Titers
Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes - Primary Phase of the Study
Titers10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
OPA-1 At Month 338.6 (24.6 to 60.5)27.8 (17.5 to 44.2)29.4 (19.4 to 44.5)68.9 (47.5 to 99.9)
OPA-4 At Month 3703.7 (533.5 to 928.2)844.4 (660.8 to 1079.0)819.2 (652.7 to 1028.1)748.1 (509.9 to 1097.5)
OPA-5 At Month 347.3 (33.6 to 66.6)60.6 (44.1 to 83.3)50.3 (37.2 to 68.1)72.9 (52.2 to 101.8)
OPA-6B At Month 3399.6 (249.4 to 640.4)454.7 (299.8 to 689.7)409.7 (251.0 to 668.7)884.9 (569.3 to 1375.5)
OPA-7F At Month 33212.6 (2434.8 to 4238.8)3697.6 (2748.6 to 4974.1)4234.2 (3203.0 to 5597.4)7394.5 (4411.1 to 12395.7)
OPA-9V At Month 31942.4 (1381.9 to 2730.1)1520.7 (1109.4 to 2084.5)1983.6 (1507.2 to 2610.7)2242.8 (1474.7 to 3411.1)
OPA-14 At Month 31405.3 (1060.3 to 1862.4)1334.9 (1013.9 to 1757.4)1575.3 (1143.5 to 2170.1)2410.6 (1516.6 to 3831.5)
OPA-18C At Month 3108.1 (72.6 to 161.2)102.7 (70.3 to 150.0)169.4 (121.9 to 235.4)257.6 (179.4 to 369.9)
OPA-19F At Month 3211.6 (139.6 to 320.7)344.1 (240.6 to 492.0)381.6 (256.8 to 566.9)142.5 (98.9 to 205.4)
OPA-23F At Month 31275.6 (771.1 to 2110.3)2170.3 (1559.9 to 3019.6)1757.9 (1191.4 to 2593.7)4437.1 (2874.9 to 6848.2)
OPA-3 (At Month 35.0 (3.9 to 6.4)4.5 (3.9 to 5.2)4.6 (4.0 to 5.3)88.4 (67.3 to 116.0)
OPA-6A At Month 343.2 (23.8 to 78.5)59.6 (35.4 to 100.3)44.7 (26.2 to 76.2)1726.0 (1113.9 to 2674.4)
OPA-19A At Month 3576.0 (340.6 to 974.3)914.6 (586.8 to 1425.6)905.2 (628.2 to 1304.5)2915.3 (2270.3 to 3743.6)
SecondaryTiters for Opsonophagocytic Activity Against Pneumococcal Serotypes - Booster Phase of the Study

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The Seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · Titers
Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes - Booster Phase of the Study
Titers10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
OPA-1 Month 1012.4 (7.6 to 20.1)13.2 (8.3 to 21.1)18.7 (11.2 to 31.4)10.3 (6.8 to 15.5)
OPA-1 Month 11373.5 (253.3 to 550.8)369.2 (252.8 to 539.4)300.0 (213.2 to 422.1)369.3 (281.4 to 484.6)
OPA-4 Month 1036.2 (19.1 to 68.4)48.3 (25.6 to 91.0)122.3 (75.0 to 199.6)18.5 (9.7 to 35.4)
OPA-4 Month 111370.7 (1034.2 to 1816.6)1634.8 (1284.8 to 2080.3)2043.3 (1609.1 to 2594.6)2882.6 (2252.4 to 3689.1)
OPA-5 Month 109.3 (6.9 to 12.5)10.5 (6.9 to 16.1)9.5 (6.9 to 12.9)8.7 (6.3 to 12.0)
OPA-5 Month 11154.5 (111.8 to 213.4)166.8 (118.4 to 234.8)139.3 (102.3 to 189.8)327.4 (254.2 to 421.8)
OPA-6B Month 10103.2 (56.5 to 188.4)174.5 (102.1 to 298.2)136.9 (76.1 to 246.4)113.8 (59.3 to 218.6)
OPA-6B Month 11802.1 (531.7 to 1210.0)700.3 (481.3 to 1018.8)1013.8 (744.6 to 1380.3)2731.1 (1972.7 to 3781.1)
OPA-7F Month 10795.5 (560.1 to 1129.9)886.4 (599.1 to 1311.5)1322.5 (961.5 to 1819.1)1895.8 (1420.6 to 2530.0)
OPA-7F Month 115819.9 (4473.1 to 7572.2)5733.8 (4165.0 to 7893.5)8336.9 (6357.9 to 10931.8)18012.3 (13872.4 to 23387.7)
OPA-9V Month 10281.5 (175.4 to 451.7)340.8 (224.0 to 518.5)433.7 (318.3 to 591.0)510.4 (344.6 to 755.8)
OPA-9V Month 112001.6 (1506.6 to 2659.3)2436.5 (1734.5 to 3422.6)3711.7 (2881.2 to 4781.4)6839.2 (5464.7 to 8559.3)
OPA-14 Month 10275.8 (175.2 to 434.3)208.1 (111.9 to 386.9)355.6 (216.3 to 584.8)483.0 (286.9 to 813.1)
OPA-14 Month 112216.9 (1678.0 to 2928.9)2297.4 (1640.0 to 3218.4)2488.9 (1942.5 to 3189.0)3545.0 (2465.2 to 5097.8)
OPA-18C Month 105.1 (4.0 to 6.6)6.3 (4.6 to 8.7)6.7 (4.9 to 9.0)4.8 (3.9 to 6.1)
OPA-18C Month 11374.6 (271.2 to 517.4)303.6 (197.7 to 466.3)511.0 (356.7 to 732.2)464.4 (327.7 to 658.1)
OPA-19F Month 1018.0 (11.2 to 29.0)31.0 (19.2 to 49.9)30.7 (19.2 to 49.2)7.4 (4.8 to 11.5)
OPA-19F Month 11650.2 (444.1 to 951.9)778.9 (500.4 to 1212.3)1053.9 (812.6 to 1366.8)767.1 (582.1 to 1010.9)
OPA-23F Month 10189.6 (83.5 to 430.5)281.4 (123.2 to 642.8)242.5 (106.5 to 552.2)367.4 (150.3 to 897.8)
OPA-23F Month 113621.0 (2534.5 to 5173.2)2563.6 (1831.6 to 3588.2)4465.4 (3368.6 to 5919.3)32508.0 (23754.9 to 44486.3)
OPA-3 Month 106.7 (4.7 to 9.5)8.3 (4.9 to 14.0)6.3 (4.6 to 8.8)12.0 (7.6 to 19.1)
OPA-3 Month 117.8 (5.7 to 10.6)7.8 (5.4 to 11.2)9.2 (6.8 to 12.5)333.9 (260.3 to 428.3)
OPA-6A Month 1026.5 (13.2 to 52.9)23.3 (10.3 to 53.1)18.7 (9.8 to 35.7)129.7 (61.2 to 274.7)
OPA-6A Month 11163.1 (94.0 to 283.1)190.0 (106.6 to 338.4)276.2 (174.8 to 436.6)4855.3 (3606.3 to 6536.8)
OPA-19A Month 10211.8 (139.2 to 322.4)262.0 (157.8 to 435.1)315.6 (193.5 to 514.6)776.3 (542.2 to 1111.7)
OPA-19A Month 112006.3 (1539.1 to 2615.3)2609.5 (1919.1 to 3548.2)2699.1 (2262.2 to 3220.5)7137.0 (5909.4 to 8619.6)
SecondaryConcentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid Haemolysis Activity - Primary Phase of the Study

Analysis of the concentrations of antibodies inhibiting pneumococcal pneumolysin toxoid haemolysis activity (anti-Ply) was not performed as no assay was validated to perform this analysis. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

No measurements were reported for this outcome.

SecondaryConcentrations of Antibodies Inhibiting Pneumococcal Pneumolysin Toxoid Haemolysis Activity - Booster Phase of the Study

Analysis of the concentrations of antibodies inhibiting pneumococcal pneumolysin toxoid haemolysis activity (anti-Ply) was not performed as no assay was validated to perform this analysis. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

No measurements were reported for this outcome.

SecondaryConcentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Primary Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.1 IU/mL. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · IU/mL
Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Primary Phase of the Study
IU/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-D At Month 33.251 (2.729 to 3.873)3.185 (2.556 to 3.968)3.353 (2.756 to 4.080)2.933 (2.464 to 3.492)
ANTI-T At Month 32.579 (2.187 to 3.041)2.193 (1.819 to 2.643)2.252 (1.930 to 2.627)1.416 (1.166 to 1.719)
SecondaryConcentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Booster Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.1 IU/mL. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · IU/mL
Concentrations of Antibodies Against Diphtheria (Anti-D) and Tetanus (Anti-T) - Booster Phase of the Study
IU/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-D At Month 100.731 (0.575 to 0.929)0.587 (0.461 to 0.747)0.651 (0.507 to 0.836)0.614 (0.497 to 0.758)
ANTI-D At Month 119.872 (8.191 to 11.898)8.688 (7.026 to 10.743)9.742 (7.991 to 11.878)8.290 (6.943 to 9.899)
ANTI-T At Month 100.815 (0.665 to 0.999)0.727 (0.570 to 0.927)0.726 (0.604 to 0.874)0.371 (0.280 to 0.493)
ANTI-T At Month 118.725 (7.259 to 10.488)8.703 (7.415 to 10.215)9.929 (8.653 to 11.394)5.040 (4.074 to 6.234)
SecondaryConcentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Primary Phase of the Study

Antibody concentrations will be measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs) in Elisa Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 5 EL.U/mL. This outcome concerns results for the primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Primary Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-PT At Month 369.0 (59.9 to 79.4)64.3 (54.8 to 75.3)70.0 (61.6 to 79.4)64.6 (53.2 to 78.3)
ANTI-FHA At Month 3187.9 (159.0 to 222.1)178.1 (150.2 to 211.2)157.1 (132.5 to 186.3)188.6 (156.4 to 227.5)
ANTI-PRN At Month 395.1 (79.2 to 114.4)79.5 (63.6 to 99.2)91.4 (75.2 to 111.1)87.2 (70.6 to 107.5)
SecondaryConcentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Booster Phase of the Study

Antibody concentrations will be measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs) in Elisa Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 5 EL.U/mL. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · EL.U/mL
Concentrations of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) - Booster Phase of the Study
EL.U/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-PT At Month 1017.5 (13.4 to 22.9)12.7 (9.9 to 16.3)12.1 (9.7 to 15.1)12.2 (9.6 to 15.5)
ANTI-PT At Month 1193.8 (75.4 to 116.6)90.6 (73.5 to 111.7)95.7 (80.1 to 114.3)85.2 (70.3 to 103.2)
ANTI-FHA At Month 1063.0 (50.3 to 78.9)51.7 (40.1 to 66.6)48.5 (38.3 to 61.5)54.2 (42.5 to 69.2)
ANTI-FHA At Month 11359.4 (291.3 to 443.5)380.1 (311.9 to 463.2)308.4 (252.0 to 377.3)376.7 (322.6 to 439.8)
ANTI-PRN At Month 1021.8 (15.8 to 30.1)16.1 (11.7 to 22.2)14.3 (10.7 to 19.3)14.3 (10.6 to 19.3)
ANTI-PRN At Month 11294.8 (227.0 to 382.8)228.5 (174.2 to 299.7)224.2 (180.0 to 279.1)197.3 (154.3 to 252.2)
SecondaryConcentrations of Antibodies Against Hepatitis B (Anti-HBs) - Primary Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Primary Phase of the study. Note that the percentage of subjects with concentration ≥10 mIU/mL was over-estimated due to the use of in-house assay overestimating concentrations between 10-100 mIU/mL. Accordingly GMCs were also overestimated.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · mIU/mL
Concentrations of Antibodies Against Hepatitis B (Anti-HBs) - Primary Phase of the Study
mIU/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Concentrations of Antibodies Against Hepatitis B (Anti-HBs) - Primary Phase of the Study676.7 (466.2 to 982.3)619.1 (386.5 to 991.5)719.8 (537.0 to 965.0)877.4 (597.0 to 1289.4)
SecondaryConcentrations of Antibodies Against Hepatitis B (Anti-HBs) - Booster Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Booster Phase of the study. \* A decrease in the specificity of the anti-HB Enzyme-Linked ImmunoSorbent Assay (ELISA) assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete reanalysis. The retest has been performed in using Food and Drug Administration (FDA)-approved ChemiLuminescence ImmunoAssay (CLIA) commercial assay Centaur™.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · mIU/mL
Concentrations of Antibodies Against Hepatitis B (Anti-HBs) - Booster Phase of the Study
mIU/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-HBs At Month 10299.2 (199.0 to 449.8)287.1 (195.1 to 422.4)166.6 (105.2 to 263.8)174.5 (113.5 to 268.2)
ANTI-HBs At Month 114110.9 (2576.5 to 6558.9)4234.8 (2961.4 to 6055.7)3142.4 (2151.1 to 4590.6)3116.4 (2142.5 to 4533.0)
SecondaryConcentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Primary Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.15 µg/mL or 1 µg/mL. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · µg/mL
Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Primary Phase of the Study
µg/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Primary Phase of the Study1.920 (1.433 to 2.573)1.975 (1.390 to 2.806)1.813 (1.330 to 2.472)0.963 (0.690 to 1.344)
SecondaryConcentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Booster Phase of the Study

Antibody concentrations will be expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.15 µg/mL or 1 µg/mL. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · µg/mL
Concentrations of Antibodies Against Polyribosyl Ribitol Phosphate (Anti-PRP) - Booster Phase of the Study
µg/mL10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-PRP At Month 100.390 (0.279 to 0.546)0.446 (0.306 to 0.651)0.503 (0.360 to 0.703)0.272 (0.193 to 0.384)
ANTI-PRP At Month 1116.961 (11.652 to 24.689)28.168 (20.580 to 38.554)24.549 (16.379 to 36.795)12.853 (8.301 to 19.899)
SecondaryTiters of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Primary Phase of the Study

Antibody titers will be measured by virus microneutralization test, expressed as geometric mean titers (GMTs). The cut-off of the assay for anti-1, anti-2 and anti-3 antibody was a titer higher than or equal to (≥) 8. This outcome concerns results for the Primary Phase of the study.

Time frame:
At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · Titers
Titers of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Primary Phase of the Study
Titers10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-Polio 1 At Month 3175.7 (124.5 to 247.8)138.2 (91.0 to 209.8)190.3 (115.7 to 312.9)173.7 (128.9 to 234.0)
ANTI-Polio 2 At Month 3134.3 (86.3 to 209.1)114.7 (68.6 to 192.0)177.6 (102.5 to 307.8)148.4 (101.1 to 217.9)
ANTI-Polio 3 At Month 3445.7 (290.9 to 682.9)432.2 (273.0 to 684.3)552.7 (361.1 to 846.1)538.6 (413.6 to 701.4)
SecondaryTiters of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Booster Phase of the Study

Antibody titers will be measured by virus microneutralization test, expressed as geometric mean titers (GMTs). The cut-off of the assay for anti-1, anti-2 and anti-3 antibody was a titer higher than or equal to (≥) 8. This outcome concerns results for the Booster Phase of the study.

Time frame:
At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)
Reported as:
Geometric mean · Titers
Titers of Antibodies Against Poliovirus Types 1, 2 and 3 (Anti-1, Anti-2 and Anti-3) - Booster Phase of the Study
Titers10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
ANTI-Polio 1 At Month 1041.7 (25.9 to 67.3)58.3 (35.6 to 95.6)55.5 (33.9 to 90.9)55.4 (38.3 to 80.1)
ANTI-Polio 1 At Month 111116.0 (696.1 to 1789.3)1222.0 (737.1 to 2026.1)1149.6 (764.3 to 1729.0)1233.2 (898.9 to 1691.9)
ANTI-Polio 2 At Month 1050.4 (33.4 to 76.0)55.9 (35.6 to 87.8)61.0 (40.2 to 92.7)66.8 (48.6 to 91.9)
ANTI-Polio 2 At Month 111998.1 (1415.0 to 2821.5)2332.2 (1739.0 to 3127.6)2048.3 (1484.6 to 2825.9)2284.8 (1705.1 to 3061.6)
ANTI-Polio 3 At Month 10167.7 (113.3 to 248.3)104.9 (68.7 to 160.2)125.4 (81.2 to 193.6)93.1 (66.2 to 130.9)
ANTI-Polio 3 At Month 112995.8 (2081.1 to 4312.6)3626.3 (2623.6 to 5012.2)2696.8 (1913.7 to 3800.4)2820.0 (2127.9 to 3737.4)
SecondaryNumber of Subjects With Any and Grade 3 Solicited Local Symptoms - Primary Phase of the Study

Assessed local symptoms were pain, redness and swelling at injection site. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (\>) 30 millimeters (mm).

Time frame:
Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course
Reported as:
Count of participants · Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Primary Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Any Pain, post D152465340
Grade 3 Pain, post D10230
Any Redness, post D159585251
Grade 3 Redness, post D10032
Any Swelling, post D147463437
Grade 3 Swelling, post D13536
Any Pain, post D252494243
Grade 3 Pain, post D22012
Any Redness, post D267676359
Grade 3 Redness, post D22230
Any Swelling, post D249564338
Grade 3 Swelling, post D25423
Any Pain, post D341353745
Grade 3 Pain, post D32311
Any Redness, post D365655865
Grade 3 Redness, post D33203
Any Swelling, post D352524343
Grade 3 Swelling, post D36335
SecondaryNumber of Subjects With Any and Grade 3 Solicited Local Symptoms - Booster Phase of the Study

Assessed local symptoms were pain, redness and swelling at injection site. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (\>) 30 millimeters (mm).

Time frame:
Within the 7-day (Days 0-6) period after booster vaccination
Reported as:
Count of participants · Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Booster Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Any Pain77736168
Grade 3 Pain7634
Any Redness83816866
Grade 3 Redness1115127
Any Swelling70554959
Grade 3 Swelling88710
SecondaryNumber of Subjects With Any, Grade 3 Solicited General Symptoms and Solicited General Symptoms With Relationship to Vaccination - Booster Phase of the Study

Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than \[≥\] 38 degrees Celsius \[°C\]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigator as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Axillary temperature higher than (\>) 40.0°C.

Time frame:
Within the 7-day (Days 0-6) period post vaccination after booster vaccination
Reported as:
Count of participants · Participants
Number of Subjects With Any, Grade 3 Solicited General Symptoms and Solicited General Symptoms With Relationship to Vaccination - Booster Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Any Drowsiness77646673
Grade 3 Drowsiness1511
Related Drowsiness68615969
Any Irritability95848290
Grade 3 Irritability12848
Related Irritability86827683
Any Loss Appet49383657
Grade 3 Loss Appet.3422
Related Loss Appet.42383349
Any Fever50555153
Grade 3 Fever1013
Related Fever44524547
SecondaryNumber of Subjects With Unsolicited Adverse Events (AEs) - Primary Phase of the Study

An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

Time frame:
Within the 31-day (Days 0-30) period post primary vaccination, across doses
Reported as:
Count of participants · Participants
Number of Subjects With Unsolicited Adverse Events (AEs) - Primary Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Number of Subjects With Unsolicited Adverse Events (AEs) - Primary Phase of the Study55686461
SecondaryNumber of Subjects With Unsolicited Adverse Events (AEs) - Booster Phase of the Study

An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

Time frame:
Within the 31-day (Days 0-30) period post booster vaccination
Reported as:
Count of participants · Participants
Number of Subjects With Unsolicited Adverse Events (AEs) - Booster Phase of the Study
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Number of Subjects With Unsolicited Adverse Events (AEs) - Booster Phase of the Study40262734
SecondaryNumber of Subjects With Serious Adverse Events (SAEs)

An SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of an SAE, regardless of relationship to vaccination.

Time frame:
During the entire study period (Months 0-11)
Reported as:
Count of participants · Participants
Number of Subjects With Serious Adverse Events (SAEs)
Participants10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
Number of Subjects With Serious Adverse Events (SAEs)1392117

Adverse events

Collected over Solicited symptoms: during the 7 days post-primary vaccination and post-booster vaccination. Unsolicited AEs during 31 days post-primary vaccination and post booster vaccination. SAEs: during the entire study period (Months 0-11).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
10PP-LD/Infanrix Hexa Group0/146 (0%)13/146 (8.9%)141/146 (96.6%)
10PP-HD/Infanrix Hexa Group0/142 (0%)9/142 (6.3%)137/142 (96.5%)
Synflorix/Infanrix Hexa Group0/145 (0%)21/145 (14.5%)139/145 (95.9%)
Prevnar 13/Infanrix Hexa Group0/142 (0%)17/142 (12%)134/142 (94.4%)
Most frequent serious events
Showing 10 of 48
Most frequent serious events
Event10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
BronchitisInfections and infestations1/1461/1422/1453/142
ConcussionInjury, poisoning and procedural complications0/1460/1423/1450/142
Otitis mediaInfections and infestations3/1460/1421/1450/142
LaryngitisInfections and infestations0/1461/1420/1452/142
Febrile convulsionNervous system disorders0/1460/1420/1452/142
PneumoniaInfections and infestations2/1461/1420/1451/142
GastroenteritisInfections and infestations1/1461/1421/1450/142
Gastroenteritis rotavirusInfections and infestations1/1461/1420/1451/142
Thermal burnInjury, poisoning and procedural complications1/1461/1420/1451/142
HypoglycaemiaMetabolism and nutrition disorders0/1461/1421/1450/142
Most frequent other events
Showing 10 of 20
Most frequent other events
Event10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa Group
IrritabilityGeneral disorders118/146113/142110/144113/142
DrowsinessGeneral disorders107/14696/14298/144102/142
RednessGeneral disorders96/14697/14288/14483/142
IrritabilityGeneral disorders95/14484/14082/13990/140
RednessGeneral disorders83/14481/14068/13966/140
SwellingGeneral disorders82/14674/14260/14459/142
PainGeneral disorders77/14473/14061/13968/140
DrowsinessGeneral disorders77/14464/14066/13973/140
Fever (rectal temperature >= 38°C)General disorders76/14671/14274/14465/142
PainGeneral disorders75/14673/14272/14464/142

Baseline characteristics

Age, Continuous
Age, Continuous(Weeks)10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa GroupTotal
Mean10.3 ± 2.4910.1 ± 2.7010.1 ± 2.6110.2 ± 2.6410.2 ± 2.61
Sex: Female, Male
Sex: Female, Male(Participants)10PP-LD/Infanrix Hexa Group10PP-HD/Infanrix Hexa GroupSynflorix/Infanrix Hexa GroupPrevnar 13/Infanrix Hexa GroupTotal
Female65677066268
Male81757576307
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Study locations

24 sites
  • GSK Investigational Site
    Benesov, 256 01, Czechia
  • GSK Investigational Site
    Brno, 613 00, Czechia
  • GSK Investigational Site
    Decin, 405 01, Czechia
  • GSK Investigational Site
    Jindrichuv Hradec, 37701, Czechia
  • GSK Investigational Site
    Kladno, 272 01, Czechia
  • GSK Investigational Site
    Liberec, 46015, Czechia
  • GSK Investigational Site
    Nachod, 547 01, Czechia
  • GSK Investigational Site
    Ostrov, 363 01, Czechia
  • GSK Investigational Site
    Pardubice, 532 03, Czechia
  • GSK Investigational Site
    Praha 6, 1600, Czechia
  • GSK Investigational Site
    Schwäbisch-Hall, Baden-Wuerttemberg 74523, Germany
  • GSK Investigational Site
    Tuttlingen, Baden-Wuerttemberg 78532, Germany
  • GSK Investigational Site
    Detmold, Nordrhein-Westfalen 32756, Germany
  • GSK Investigational Site
    Frankenthal, Rheinland-Pfalz 67227, Germany
  • GSK Investigational Site
    Berlin, 13055, Germany
  • GSK Investigational Site
    Debica, 39-200, Poland
  • GSK Investigational Site
    Krakow, 31-503, Poland
  • GSK Investigational Site
    Poznan, 61-709, Poland
  • GSK Investigational Site
    Siemianowice Slaskie, 41-103, Poland
  • GSK Investigational Site
    Warszawa, 01-184, Poland
  • GSK Investigational Site
    Wroclaw, 50345, Poland
  • GSK Investigational Site
    Umeå, SE-901 85, Sweden
  • GSK Investigational Site
    Örebro, SE-702 11, Sweden
  • GSK Investigational Site
    Östersund, SE-831 83, Sweden
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References and documents

Publications

  • Prymula R, Szenborn L, Silfverdal SA, Wysocki J, Albrecht P, Traskine M, Gardev A, Song Y, Borys D. Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a randomized phase II study in infants. Vaccine. 2017 Aug 16;35(35 Pt B):4603-4611. doi: 10.1016/j.vaccine.2017.07.008. Epub 2017 Jul 17. PubMed 28729019 ↗

Individual participant data

Plan to share: Yes — IPD is available via the Clinical Study Data Request site (click on the link provided below)

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 29, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01204658
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Sep 17, 2010
Start date
Sep 27, 2010
Primary completion
Nov 3, 2011
Completion
Oct 1, 2012
Results posted
Sep 28, 2016
Last update
May 29, 2019

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline
View the source record on ClinicalTrials.gov ↗

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