Co-administration of Meningococcal Vaccine GSK134612 and Pneumococcal Vaccine GSK1024850A vs Individual Administration

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate, in 12-23 months old subjects, the non-inferiority of meningococcal vaccine GSK134612 and pneumococcal vaccine GSK1024850A when co-administered, compared to each vaccine administered individually.

Detailed Description
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Multi-center study with 3 parallel groups. One group will receive 2 vaccines injections at the same visit (pneumococcal+ meningococcal), one group will receive a pneumococcal vaccine followed one month later by a meningococcal vaccine, and the last group will receive the meningococcal vaccine followed one month later by the pneumococcal vaccine. All subjects will have one blood sample taken before vaccination and one blood sample taken one month after each vaccination (i.e. the first group will have 2 blood samples taken, and the other two groups will have 3 blood sample taken)

Official Title
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Immunogenicity & Safety Study of GSK Biologicals' Meningococcal Vaccine GSK134612 When Co-administered With GSK Biologicals' Pneumococcal Vaccine GSK1024850A in Healthy 12-23-month-old Children Previously Primed With GSK1024850A

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612
* 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. A male or female between, and including, 12 and 23 months of age at the time of the first booster vaccination, who previously participated in study 109661 conducted in Mexico or in study 109861 conducted in Taiwan and who received 3 doses of the GSK1024850A vaccine. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects 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 vaccines within 30 days preceding the first dose of study vaccine(s), or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine(s) and 30 days after the last dose of vaccine(s). 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). Previous vaccination with a meningococcal vaccine. Previous administration of a fourth dose of a pneumococcal vaccine Previous vaccination with tetanus toxoid within the last month (including also tetanus toxoid given as part of Hib-TT conjugate vaccine). History of meningococcal or pneumococcal invasive disease. History of reactions or allergic disease likely to be exacerbated by any component of the vaccines. Hypersensitivity reaction due to previous vaccination with GSK1024850A vaccine. History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical examination (no laboratory testing required). A family history of congenital or hereditary immunodeficiency, unless the child has previously been documented, through laboratory testing, to have normal immune function. Major congenital defects or serious chronic illness. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

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>Meningococcal vaccine GSK134612 co-administered with pneumococcal vaccine GSK1024850A. | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection.<br>Biological: Pneumococcal vaccine GSK1024850A<br>* Single dose intramuscular injection.<br>|
| Active Comparator: Group B<br>Pneumococcal vaccine GSK1024850A followed one month later by meningococcal vaccine GSK134612. | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection.<br>Biological: Pneumococcal vaccine GSK1024850A<br>* Single dose intramuscular injection.<br>|
| Active Comparator: Group C<br>Meningococcal vaccine GSK134612 followed one month later by pneumococcal vaccine GSK1024850A. | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection.<br>Biological: Pneumococcal vaccine GSK1024850A<br>* Single dose intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-pneumococcal Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). Anti-pneumococcal serotypes assessed were Anti-1, Anti-4, Anti-5, Anti-6B, Anti-7F, Anti-9V, Anti-14, Anti-18C, Anti-19F and Anti-23F via the 22F-inhibition Enzyme Linked Immunosorbent Assay (ELISA). | At Month 1 | 
| Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C , W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW -135 and rSBA-Men-Y) Antibody Titers Greater Than or Equal to (≥) the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8. | At Month 1 | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-Men-Y Antibody Titers | Antibody titers are presented as geometric mean titers (GMTs) and are measured in titers. | At Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-pneumococcal Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). The 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) via 22F-inhibition ELISA. GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE) and at one month post dose 2 (Month 2) | 
| Cross-reactive Anti-pneumococcal Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in µg/mL. The pneumococcal serotypes assessed were 6A and 19A (anti-6A and anti-19A) via the 22F-inhibition ELISA. GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2) | 
| Opsonophagocytic Titers Against Pneumococcal Serotypes | Opsonophagocytic titers are presented as geometric mean titers (GMTs). The 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). GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2) | 
| Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes | Opsonophagocytic titers are presented as geometric mean titers (GMTs). The pneumococcal serotypes assessed were 6A and 19A (OPSONO-6A and OPSONO-19A). GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2) | 
| Anti-protein D (Anti-PD) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1(Month 1) and at one month post dose 2 (Month 2) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW -135 and rSBA-Men-Y Antibody Titers | Antibody titers are presented as geometric mean titers (GMTs) and measured in titers. GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE) and at one month post dose 2 (Month 2) | 
| Anti-meningococcal Polysaccharide (Anti-PS) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2) | 
| Anti-tetanus (Anti-T) Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose. | Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the 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. | Within the 4-day (Days 0-3) post-vaccination period after each dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [defined as rectally temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activities. 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 higher than (>) 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within the 4-day (Days 0-3) post-vaccination period after each dose | 
| 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 the 31-day (Day 0-30) post-vaccination period after each dose | 
| 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. | Throughout the entire study duration (Day 0-Month 7) | 
| Number of Subjects Reporting Rash | Rash-like symptoms assessed were hives, idiopathic thrombocytopenic purpura, petechiae. | Throughout the entire study duration (Day 0-Month 7) | 
| Number of Subjects With New Onset Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | Throughout the entire study duration (Day 0-Month 7) | 
| Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits | Among AEs prompting emergency room visits were: infections, injuries, skin diseases, gastrointestinal symptoms. | Throughout the entire study duration (Day 0-Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Routine infancy vaccination, Meningococcal vaccine, Immunogenicity, Pneumococcal vaccine