Assessment of Antibody Persistence in Children Previously Vaccinated With Pneumococcal Conjugate Vaccine

Phase 3

Completed

• Conditions: Infections, Streptococcal; Streptococcus Pneumoniae Vaccines
• Interventions: Biological: GSK1024805A; Biological: Prevenar; Biological: Infanrix hexa; Biological: Havrix; Biological: Varilrix

• Registration Number: NCT00624819
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This protocol posting deals with objectives \& outcome measures of the extension phase up to 48-50 months post booster vaccination, to assess long-term antibody persistence in children at around 30, 42 and 66 months of age, who received previously 4 doses of pneumococcal conjugate vaccine. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00307554). This Protocol posting has been updated in order to comply with the FDA AA (Sep 2007).

Detailed Description

This study consists in a serological follow-up study to evaluate persistence 12, 24 and 48 months after the booster vaccination study (107046). No study vaccines will be administered within this study.

Study Timeline

• Study First Submitted: 2008-02-15
• Study First Submitted QC: 2008-02-25
• Study First Posted: 2008-02-27
• Study Start: 2008-03-03
• Primary Completion: 2008-06-02
• Study Completion: 2008-06-02
• Disposition First Submitted: 2012-07-24
• Disposition First Submitted QC: 2012-07-24
• Disposition First Posted: 2012-08-02
• Results First Submitted: 2017-08-25
• Results First Submitted QC: 2020-03-04
• Results First Posted: 2020-03-18
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-11
• Last Update Posted: 2021-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 524

Inclusion Criteria

• Male or female between, and including, 28-30 months of age at the time of first blood sampling.
• Subjects who previously participated in the 105553 and 107046 studies and who received a full four dose regimen of pneumococcal conjugate vaccine during the primary and booster studies.
• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• Written informed consent, covering visits 1, 2 and 3, obtained from the parent or guardian of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria

• Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the blood sampling
• Administration of any additional pneumococcal vaccine since end of 107046 study.
• Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the blood sampling.
• Administration of immunoglobulins and/or any blood products less than 6 months prior to blood sampling.
• Any confirmed or suspected immunosuppressive or immunodeficient condition since the end of the 107046 study, based on medical history and physical examination.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prevenar + Infanrix + Havrix and/or Varilrix Group	Havrix	This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Synflorix + Infanrix + Havrix and/or Varilrix Group	GSK1024805A	This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Synflorix + Infanrix + Havrix and/or Varilrix Group	Havrix	This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar	This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	GSK1024805A	This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Synflorix + Infanrix + Havrix and/or Varilrix Group	Varilrix	This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Prevenar + Infanrix + Havrix and/or Varilrix Group	Varilrix	This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Havrix	This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Synflorix + Infanrix + Havrix and/or Varilrix Group	Infanrix hexa	This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Prevenar + Infanrix + Havrix and/or Varilrix Group	Infanrix hexa	This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Varilrix	This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Unprimed Group	GSK1024805A	This group consisted of subjects between, and including, 64-68 months of age at the time of additional vaccination (primed subjects) or dose 1 (unprimed subjects), and for whom the investigator believed that their parents/guardians could and would comply with the requirements of the protocol. Subjects were not previously vaccinated with any pneumococcal vaccine and received 2 doses of Synflorix vaccine at 64-68 and 66-70 months of age (at Day 0 and Month 2). The Unprimed Group was added only in Year 4 of the study.
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Prevenar	This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Infanrix hexa	This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations ≥ the Cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 μg/mL as seropositivity cut off.
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations Greater Than or Equal to (≥) the Cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 microgram per milliliter (µg/mL) as seropositivity cut off.
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations ≥ the Cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme -linked immunosorbent assay (ELISA), using 0.05 μg/mL as seropositivity cut off.

Secondary Outcome Measures

Name	Time	Method
Antibody Concentrations Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL).The seropositivity cut-off for the assay was ≥ 0.05 µg/mL.
Antibody Concentrations Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	Anti-pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F . Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.
Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) - Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)	At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PDDIT- 007)	The seropositivity cut-off for the assay was ≥ 0.05 μg/mL. Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micrograms per milliliter (µg/mL).
Antibody Concentrations Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PDDIT- 007)	Pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.
Antibody Concentrations Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 µg/mL.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	Pneumococcal serotypes assessed were OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	The seropositivity cut-off for the assay was ≥ 0.05 μg/mL. Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micrograms per milliliter (µg/mL).
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007)	Pneumococcal serotypes assessed were OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	Opsonophagocytic activity were assessed for pneumococcal serotypes 6A and 19A (OPA-6A and OPA-19A). The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Antibody Concentrations to Protein D (Anti-PD) - Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT- 007)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were mesured by Opsonophagocytic activity (OPA). The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	Pneumococcal serotypes assessed were OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007)	Opsonophagocytic activity were assessed for pneumococcal serotypes 6A and 19A (OPA-6A and OPA-19A). The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	Opsonophagocytic activity were assessed for pneumococcal serotypes 6A and 19A (OPA-6A and OPA-19A). The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Antibody Concentrations to Protein D (Anti-PD) - Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.
Number of Subjects With Serious Adverse Events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 Sub-study)]	For primed groups: from Months 48-49 (additional vaccination period); for unprimed group: from Day 0 up to Month 3 (catch-up vaccination period)	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" is defined an incidence of a SAE regardless of intensity/severity.
Number of Seropositive Subjects for Opsophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Analysis was performed with Unprimed group included. The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT-007)	Pneumococcal serotypes assessed were pneumococcal serotypes OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.
Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	Opsonophagocytic activity were assessed for pneumococcal serotypes 6A and 19A (OPA-6A and OPA-19A). The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).
Number of Subjects With Unsolicited Adverse Events (AEs)	Within 31 days (Day 0-30) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study	An AE is 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. "Any" was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Follow-up period was of 31 days (Days 0-30) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 31 days for primed subjects and 2 periods of 31 days for unprimed subjects.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic Activity (OPA). The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.
Number of Seropositive Subjects for Anti-vaccine Pneumococcal Serotypes Antibodies [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 microgram per milliliter (µg/mL) as seropositivity cut off.
Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT- 007)	Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.
Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibation ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.
Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic Activity (OPA). The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti Protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 2 (111345 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.
Antibody Concentrations to Protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT- 007)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.
Antibody Concentrations to Protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)]	For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.
Number of Subjects Reported With Solicited Local Symptoms	Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study	Solicited local symptoms assessed were pain, redness and swelling. Any occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom greater than (\>) 0 millimeter (mm). Grade 3 pain = maximum intensity of local injection defined as subject crying when limb was moved/spontaneously painful. Grade 3 redness/swelling= maximum intensity of local injection \>30 mm. Follow-up period was of 4 days (Days 0-3) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 4 days for primed subjects and 2 periods of 4 days for unprimed subjects.
Number of Subjects Reported With Solicited General Symptoms	Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study	Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (any fever defined as temperature by axillary measurement of 37.5°C and above). Grade 3 drowsiness was defined as drowsiness that prevented normal activity; Grade 3 irritability was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as subject not eating at all. Grade 3 fever was defined as axillary temperature \>39.5°C. Related AE was defined as any AE assessed by investigators to be causally related to administration of the study vaccine. Follow-up period was of 4 days (Days 0-3) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 4 days for primed subjects and 2 periods of 4 days for unprimed subjects.
Number of Subjects With Serious Adverse Events (SAEs) Related to Study Procedures [Follow-up Period: Year 1 (111345 Sub-study)]	During Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007) i.e. for each primed subject: from the time the subject was enrolled in the 111345 study until he/she completed the same study (approximatively 12 months)	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" was defined an incidence of a SAE regardless of intensity/severity.
Number of Subjects With Serious Adverse Events (SAEs) Related to Study Procedures [(Follow-up Period: Year 2 (111346 Sub-study) Until Year 4 (111347 Sub-study)]	From Year (Y) 2 to Y4 FU visit (post booster vaccination administered in 10PN-PD-DIT-007) i.e. for each subject(S): when S was enrolled in 111346 study until S completed the same study visit or the 111347 study visit (range of 1 to 3 years for each S))	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" is defined an incidence of a SAE regardless of intensity/severity.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]	At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The results for the immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.
Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]	At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic activity (OPA). The seropositivity cut-off for the assay was 8.
Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]	At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)	A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.

Trial Locations

Locations (1)

GSK Investigational Site; 🇵🇱 Siemianowice Slaskie, Poland