Study to Evaluate Persistence of Antibodies After Vaccination With Meningococcal Vaccine GSK134612

Study Overview
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Brief Summary
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Subjects were previously vaccinated at 12 to 23 months of age. This extension study starts 24 months after vaccination and the subjects who were vaccinated in the primary study will be enrolled in this extension phase. No new subjects will be enrolled.

Detailed Description
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This study will assess the long-term protection offered by the new meningococcal vaccine GSK 134612 compared to Meningitec™ up to 4 years after vaccination of toddlers. Subjects were previously vaccinated at 12 to 23 months of age with GSK Biologicals' meningococcal vaccine GSK 134612 or Meningitec™. All subjects received at least one dose of Priorix-Tetra™. This extension phase starts 24 months after vaccination and the subjects who were vaccinated in the primary study will be enrolled in this extension study. No new subjects will be enrolled. The subjects will have a blood sample taken at 24, 36 and 48 months after primary vaccination. At Year 4 subjects will be boosted with the same meningococcal vaccine as given in the primary study, i.e. either the new meningococcal vaccine GSK 134612 or Meningitec™. Blood samples will be taken 1 and 12 months after the booster vaccination.

Official Title
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Persistence of Antibodies After GSK Biologicals' Meningococcal Vaccine GSK134612 in Toddlers

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612
* Biological: Meningitec™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol should be enrolled in the study. Written informed consent obtained from the parent(s) or guardian(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. A male or female having completed the primary study 109670 and who was primed with the investigational or Meningitec™ vaccines. Exclusion Criteria: Exclusion criteria for persistence study entry (i.e. Month 24, 36 or 48): Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the subject's first visit. History of meningococcal disease. Administration of a meningococcal polysaccharide or a meningococcal polysaccharide conjugate vaccine outside of study 109670. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history. Administration of immunoglobulins and/or blood products within the three months preceding the subjects first visit. Concurrently participating in another clinical study, within 30 days of study entry, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy. Additional exclusion criteria for booster vaccination (to be checked at Month 48): Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Hypersensitivity to any vaccine containing diphtheria toxoid or non-toxic diphtheria toxin protein and/or tetanus toxoid. History of hypersensitivity after previous administration of Meningitec or the investigational vaccines in study 109670. Hypersensitivity to latex. Planned administration/ administration of a vaccine not foreseen by the protocol within one month before and 30 days after the booster dose. Previous vaccination with any component of the vaccines within the last month. History of any neurological disorder or seizures (one episode of febrile convulsion does not constitute an exclusion criteria). Major congenital defects or serious chronic illness. Acute disease at the time of vaccination.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects who received GSK vaccine 134612 in the primary vaccination study 109069 and will be boosted 4 years after primary vaccination with the same meningococcal vaccine as given in the primary study. | Biological: Meningococcal vaccine GSK134612<br>* One intramuscular dose (Booster)<br>|
| Active Comparator: Group B<br>Subjects who received Meningitec™ vaccine in the primary vaccination study 109069 and will be boosted 4 years after primary vaccination with the same meningococcal vaccine as given in the primary study. | Biological: Meningitec™<br>* One intramuscular dose (Booster)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serum Bactericidal Assay /Activity (rSBA) Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (Using Baby Rabbit Complement) Titres ≥ the Cut-off | The cut-off value for the assay was greater than or equal to (≥) 1:8, as measured at the GlaxoSmithKline (GSK) laboratory. | At Month 24 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:8. The analysis of this endpoint was performed by GSK. | At Month 36 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:8. The analysis of this endpoint was performed by GSK. | At Month 48 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres | The cut-off value for the assay was ≥ 1:8. The rSBA-MenA results for the Year 3 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 36 post-primary vaccination. | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres | The cut-off value for the aasay was ≥ 1:8. The rSBA-MenA results for the Year 4 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 48 post-primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBAMenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:128, as measured at the GlaxoSmithKline (GSK) laboratory. | At Month 24 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:128. The analysis of this endpoint was performed by GSK. | At Month 36 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:128. The analysis of this endpoint was performed by GSK. | At Month 48 post primary vaccination | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | The results for the assay were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres, as measured at the GlaxoSmithKline (GSK) laboratory | At Months 24 post primary vaccination | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres. The analysis of this endpoint was performed by GSK. | At Month 36 post primary vaccination | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres. The analysis of this endpoint was performed by GSK. | At Month 48 post primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBAMenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off for the assay was ≥ 1:128. rSBA-MenA, MenC, MenW and MenY results for the Year 3 time point obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 36 post-primary vaccination | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off value for the assay was ≥ 1:128. rSBA-MenA, MenC, MenW and MenY results for the Year 4 time point obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 48 post-primary vaccination | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres. rSBA-MenA, MenC, MenW and MenY results for the Year 3 time point obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 36 post-primary vaccination | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres. rSBA-MenA, MenC, MenW and MenY results for the Year 4 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 48 post-primary vaccination | 
| Number of Subjects With Serum Bactericidal Assay/Activity Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (Using Human Complement) Titres ≥ the Cut-off | The cut-off values for the assay were ≥ 1:4 and 1:8, respectively. The analysis of this endpoint was performed by GSK. | At Month 24 post primary vaccination | 
| Number of Subjects With Serum Bactericidal Assay/Activity Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (Using Human Complement) Titres ≥ the Cut-off | The cut-off for the assay were ≥ 1:4 and 1:8. The analysis of this endpoint was performed by GSK. | At Month 36 post primary vaccination | 
| Number of Subjects With Serum Bactericidal Assay/Activity Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (Using Human Complement) Titres ≥ the Cut-off | The cut-off for the assay were ≥ 1:4 and 1:8, as assessed by the GSK laboratory. | At Month 48 post primary vaccination | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres | The results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres, as assessed by the GSK laboratory. | At Month 24 post primary vaccination | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres | The results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres, as assessed by the GSK laboratory. | At Month 36 post primary vaccination | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres | The results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres, as measured by GSK. | At Month 48 post primary vaccination | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off values for the assay were ≥ 0.3 microgram per milliliter (μg/mL) and ≥ 2.0 μg/mL, respectively, as measured at the GlaxoSmithKline (GSK) laboratory. | At Month 24 post primary vaccination | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off values for the assay were ≥ 0.3 μg/mL and ≥ 2.0 μg/mL, respectively, as measured by the GSK laboratory. | At Month 36 post primary vaccination | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off values for the assay were ≥ 0.3 μg/mL and ≥ 2.0 μg/mL, respectively, as measured by GSK. | At Month 48 post primary vaccination | 
| Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expressed in μg/mL, as measured at the GlaxoSmithKline (GSK) laboratory. | At Month 24 post primary dose | 
| Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expresssed in μg/mL, as measured by GSK. | At Month 36 post primary vaccination | 
| Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expresssed in μg/mL, as measured by GSK. | At Month 48 post primary dose | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off values for the assay were ≥ 0.3 μg/mL and ≥ 0.2 μg/mL. Anti-PS results for the Year 3 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 36 post-primary vaccination | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off values for the assay were ≥ 0.3 μg/mL and ≥ 2.0 μg/mL, respectively. Anti-PS results for the Year 4 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 48 post-primary vaccination | 
| Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in μg/mL. Anti-PS results for the Year 3 time point were obtained by re-testing the samples in parallel at Public Health England (PHE). Results were tabulated as geometric mean antibody concentration calculated on all subjects, expressed in μg/mL. | At Month 36 post-primary vaccination | 
| Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expressed in μg/mL. Anti-PS results for the Year 4 time point obtained by re-testing the samples in parallel at Public Health England (PHE). | At Month 48 post-primary vaccination. | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres ≥ the Cut-off | The cut-off values for the assay were 1:8 and 1:128, as measured by the PHE laboratory. | At one month (Month 49) post booster dose | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres Above the Cut-off Values | The cut off values for the assay were 1:8 and 1:128, as measured by the PHE laboratory. | At 12 months (Month 60) post booster dose | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre calculated on all subjects, expressed in titres, as measured by the PHE laboratory. | At one month (Month 49) post booster dose | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titres | Results were tabulated as geometric mean antibody titre (GMT) calculated on all subjects, as measured by the PHE laboratory. | At 12 months (Month 60) post booster dose | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres Above the Cut-off Values | The cut off values for the assay were ≥ 1:4 and ≥ 1:8 respectively, as measured by GSK. | At one month (Month 49) post booster dose | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres Above the Cut-off Values | The cut off values for the assay were ≥ 1:4 and ≥ 1:8, respectively, as measured by GSK. | At 12 months (Month 60) post booster dose. | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres | The results were tabulated as geometric mean antibody titre (GMT) calculated on all subjects, expressed in titres, as measured by GSK. | At one month (Month 49) post booster dose | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titres | The results were tabulated as geometric mean antibody titre (GMT) calculated on all subjects, expressed in titres, as measured by GSK. | At 12 months (Month 60) post booster dose | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Above the Cut-off Values | The cut-off values for the assay were 0.3 μg/mL and 2.0 μg/mL, as measured by the PHE laboratory. | At one month (Month 49) post booster dose | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off Values | The cut-off for the assay were 0.3 μg/mL and 2.0 μg/mL, as measured by the PHE laboratory. | At 12 months (Month 60) post booster dose | 
| Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expressed in μg/mL, as measured by the PHE laboratory. | At one month (Month 49) post booster dose | 
| Anti-PSA, Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results were tabulated as geometric mean antibody concentration calculated on all subjects, expressed in μg/mL, as measured by the PHE laboratory. | At 12 months (Month 60) post booster dose | 
| Number of Subjects Reporting Any Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of any local symptom regardless of intensity grade. | During the 8-day period (Days 0-7) after booster vaccination | 
| Number of Subjects Reporting Any Solicited General Symptoms | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite, temperature (measured orally). Any was defined as occurrence of any general symptoms, regardless of their intensity grade or their relationship to vaccination | During the 8-day period (Days 0-7) after the booster vaccination | 
| Number of Subjects Reporting Any Adverse Events (AEs) | Any was defined as the occurrence of any adverse event regardless of intensity grade or relation to vaccination. 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 regard-less of intensity grade or relation to vaccination. | During the 31-day period (Days 0-30) after booster vaccination | 
| Number of Subjects Reporting Any 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. | At Month 24 post primary dose | 
| Number of Subjects Reporting Any 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. | At Month 36 | 
| Number of Subjects Reporting Any 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. | At Month 48 | 
| Number of Subjects Reporting Any 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. | From month 48 to month 49 (post booster follow up period) | 
| Number of Subjects Reporting Any 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. | From month 49 to month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal vaccine GSK134612