Long-term Follow-up Study of Children Previously Primed With GSK Pneumococcal Vaccine (GSK1024850A) and of Unprimed Children

Study Overview
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Brief Summary
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The objective of this study is to evaluate the immune memory through the administration of an additional dose of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A, the antibody persistence and long-term effect on nasopharyngeal carriage of S. pneumoniae and H. influenzae in subjects primed and boosted with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A in previous primary and booster studies. For subjects that did not receive the investigational vaccine during the primary and booster study, the objective is to evaluate immunogenicity, safety and reactogenicity of a 2-dose catch-up vaccination with GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A. This protocol posting deals with objectives & outcome measures of the extension phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00370318). The objectives & outcome measures of the booster phase are presented in a separate protocol posting (NCT00496015).

Detailed Description
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This protocol posting has been updated according to Protocol Amendment 1, July 2009

Official Title
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Vaccination Course in Children Primed and Boosted With Pneumococcal Vaccine GSK 1024850A and in Age-matched Unprimed Children

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK1024850A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol should be enrolled in the study. A male or female between, and including, 31 and 34 months of age at the time of the enrolment. Subjects who previously participated in study NCT00496015 For the subjects in the primed AP-AP and NAP-pre groups: subjects who received a booster dose of the pneumococcal conjugate vaccine prior to the study amendment 3. For the subjects in the unprimed group: subjects who received a dose of the meningococcal vaccine GSK134612. Written informed consent 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: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding enrolment, or planned use during the entire study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the entire study period. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of study vaccine and ending 30 days after. 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 (pharmaceutical product or device). Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. History of seizures or progressive neurological disease. Acute disease at the time of enrolment, defined as the presence of a mild, moderate or severe illness with or without fever. Administration or planned use of immunoglobulins and/ or any blood products during the entire study period. A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. Subjects of which both parents have a history of atopia (polinosis, asthma, atopic eczema). Administration of any pneumococcal vaccine since the end of study NCT00496015.

Ages Eligible for Study
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Minimum Age: 31 Months
Maximum Age: 44 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AP-AP Group<br>subjects from the AP-AP group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015, receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment | Biological: Pneumococcal vaccine GSK1024850A<br>* 1 or 2 intramuscular injections<br>|
| Active Comparator: NAP-pre Group<br>subjects from the NAP-pre group, previously vaccinated with pneumococcal conjugate vaccine GSK1024850A in study NCT00496015 receiving an additional dose of pneumococcal conjugate vaccine GSK1024850A for immune memory assessment | Biological: Pneumococcal vaccine GSK1024850A<br>* 1 or 2 intramuscular injections<br>|
| Active Comparator: Unprimed Group<br>Age-matched subjects from the unprimed group of the NCT00496015 study, not previously vaccinated with any pneumococcal vaccine, receiving two doses of pneumococcal conjugate vaccine GSK1024850A | Biological: Pneumococcal vaccine GSK1024850A<br>* 1 or 2 intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL. | At 7-10 days after the first vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Vaccine Pneumococcal Serotypes | Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL. | Prior to the first study vaccine dose (At Day 0) | 
| Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). | Prior to (Day 0) and 7-10 days after the first vaccine dose | 
| Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. | Prior to (Day 0) and 7-10 days after the first vaccine dose | 
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs). | Prior to (Day 0) and 7-10 days after the first vaccine dose | 
| Antibody Concentrations Against Protein D (Anti-PD) | Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL. | Prior to (Day 0) and 7-10 days after the first vaccine dose | 
| Memory B-cell Detection for Vaccine Polysaccharides (PS) | B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population. | Prior to (Day 0) and 7-10 days after the first vaccine dose | 
| Antibody Concentrations Against Vaccine Pneumococcal Serotypes | The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs), expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. | At Month 12, one month after the second vaccine dose | 
| Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes | Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). | At Month 12, one month after the second vaccine dose | 
| Antibody Concentrations Against Vaccine Pneumococcal Cross-reactive Serotypes 6A and 19A | The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. | At Month 12, one month after the second vaccine dose | 
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A | Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs). | At Month 12, one month after the second vaccine dose | 
| Antibody Concentrations Against Protein D (Anti-PD) | Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL. | At Month 12, one month after the second vaccine dose | 
| Rabbit Complement-mediated Serum Bactericidal Activity Titers Against Neisseria Meningitidis Serogroups (rSBA-Men) | The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8. | At 25-36 months post-vaccination in previous 107137 (NCT00496015) study | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the unprimed group. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship 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 = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship 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 = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the unprimed group. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | Within 31 days (Days 0-30) after each vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (from Day 0 up to Month 10 or Month 12) | 
| Number of Nasopharyngeal Swabs With Streptococcus Pneumoniae (Vaccine Serotypes) | Positive cultures of S. pneumoniae Synflorix™ vaccine serotypes identified in the nasopharynx were recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes) | Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) | Positive cultures of S. pneumoniae non- Synflorix™ vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Nasopharyngeal Swabs With Haemophilus Influenzae | Positive cultures of H. influenzae identified in the nasopharynx were recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Subjects With New Acquisition of S. Pneumoniae (Vaccine Serotypes) in Nasopharyngeal Swabs | The number of subjects with new acquisition of S. pneumoniae (Synflorix™ vaccine serotypes) detected in nasopharyngeal swabs was recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Subjects With New Acquisition of S. Pneumoniae (Cross-reactive Serotypes) in Nasopharyngeal Swabs | The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Subjects With New Acquisition of S. Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes) in Nasopharyngeal Swabs | The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 
| Number of Subjects With New Acquisition of H. Influenzae in Nasopharyngeal Swabs | The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded. | At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Catch-up vaccination, Pneumococcal vaccine, Immune memory, Nasopharyngeal carriage, Immunogenicity, Pneumococcal disease, Safety