Comparison of GlaxoSmithKline (GSK)134612 in Subjects With Increased Risk for Meningococcal Disease Versus Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to investigate the immunogenicity, reactogenicity and safety of the new meningococcal vaccine 134612 in subjects with increased risk of meningococcal disease and compare it to its activity in healthy subjects.

Detailed Description
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For each at risk subject enrolled, an age-matched healthy subject will be enrolled. Age matching will be performed according to the following age strata: 1-5 years, 6-10 years, 11-17 years.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Administered to at Risk Subjects From 1 to Less Than 18 Years

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol. A male or female 1 to 17 years of age at the time of the first vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrolment. Female subjects of non-childbearing potential may be enrolled in the study. Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for one month (30 days) prior to the first vaccine dose, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception from administration of the first vaccine dose until 2 months after administration of the second vaccine dose. Additional inclusion criterion for At-risk group • Subjects with an increased risk for meningococcal disease, such as anatomic asplenia or some degree of functional asplenia or complement deficiencies. Additional inclusion criteria for Healthy group Healthy subject as established by medical history and clinical examination before entering into the study. Age-matched to a subject from the At-risk group according to age strata 1-5 years, 6-10 years and 11 to 17 years. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (until the phone contact at Month 8). Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before administration of each study vaccine dose until 30 days after administration of each study vaccine dose. Administration of licensed inactivated influenza vaccines is allowed as per local recommendations. 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. History of meningococcal disease. Any confirmed or suspected Human Immunodeficiency Virus (HIV) infection, based on medical history and physical examination. Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine until one month after the second dose of study vaccine. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine including latex. Major congenital defects. History of any neurological disorders or seizures, including Guillain-Barré syndrome (GBS). History of a simple, single febrile seizure is permitted. Acute disease and/or fever at the time of enrolment. Pregnant or lactating female. History of chronic alcohol consumption and/or drug abuse. Female planning to become pregnant or planning to discontinue contraceptive precautions. Additional exclusion criteria for the At-risk group • Vaccination against meningococcal disease of any serogroup within the last 3 years for subjects younger than 7 years. within the last 5 years for subjects 7 years and older. Additional exclusion criteria for the Healthy group Vaccination against meningococcal disease of any serogroup with polysaccharide or conjugate vaccine within the last 5 years. Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose. Family history of congenital or hereditary immunodeficiency. Any confirmed or suspected immunosuppressive or immunodeficient condition. Serious chronic illness. History of asplenia or hyposplenia or complement deficiencies.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

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 |
| --- | --- |
| Experimental: Healthy Group<br>The subjects in the Healthy group will be age-matched to the subjects in the At-risk group. Subjects will receive 2 doses of the investigational vaccine. | Biological: Meningococcal vaccine GSK134612<br>* 2 doses of the vaccine administered intramuscularly in the anterolateral thigh muscle of the non-dominant leg for subjects aged 12 months to 2 years and in the deltoid of the non-dominant arm for older subjects.<br>|
| Experimental: At-risk Group<br>This group includes subjects with medical conditions placing them at an increased risk for meningococcal disease. Subjects will receive 2 doses of the investigational vaccine. | Biological: Meningococcal vaccine GSK134612<br>* 2 doses of the vaccine administered intramuscularly in the anterolateral thigh muscle of the non-dominant leg for subjects aged 12 months to 2 years and in the deltoid of the non-dominant arm for older subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Vaccine Response for Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY) Antibodies | Vaccine response was defined as: rSBA antibody titers greater than or equal to (≥) 1:32, for initially seronegative subjects [i.e. pre-vaccination rSBA antibody titers below (<) 1:8] and at least a 4-fold increase in rSBA antibody titers from pre to post-vaccination, for initially seropositive subjects (i.e. pre-vaccination rSBA antibody titers ≥ 1:8). | One month after the first vaccine dose (at Month 1) | 
| Number of Subjects With a Vaccine Response for Serum Bactericidal Assay Using Human Complement Against N. Meningitides Serogroups A, C, W-135 and Y (hSBA-MenA, hSBA-MenC, hSBA-MenW-135, hSBA-MenY) Antibodies | Vaccine response was defined as: hSBA antibody titers ≥ 1:8, for initially seronegative subjects (i.e. pre-vaccination rSBA antibody titers < 1:4) and at least a 4-fold increase in hSBA antibody titers from pre to post-vaccination, for initially seropositive subjects (i.e. pre-vaccination rSBA antibody titers ≥ 1:4). | One month after the first vaccine dose (at Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Vaccine Response for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibodies | Vaccine response was defined as: rSBA antibody titers ≥ 1:32, for initially seronegative subjects (i.e. pre-vaccination rSBA antibody titers < 1:8) and at least a 4-fold increase in rSBA antibody titers from pre to post-vaccination, for initially seropositive subjects (i.e. pre-vaccination rSBA antibody titers ≥ 1:8). | One month after the second vaccine dose (At Month 3) | 
| Number of Subjects With a Vaccine Response to hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibodies | Vaccine response was defined as: hSBA antibody titers ≥ 1:8, for initially seronegative subjects (i.e. pre-vaccination rSBA antibody titers < 1:4) and at least a 4-fold increase in hSBA antibody titers from pre to post-vaccination, for initially seropositive subjects (i.e. pre-vaccination rSBA antibody titers ≥ 1:4). | One month after the second vaccine dose (At Month 3) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Titers ≥ the Cut-off Values | The cut-off value for the assay was ≥ 1:8. | At pre-primary vaccination (Month 0), at post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Titers ≥ the Cut-off Values | The cut-off value for the assay was ≥ 1:128. | Pre-primary vaccination at Month 0, post first vaccine dose at Month 1 and post second vaccine dose at Month 3 | 
| Antibody Titers for rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Meningococcal Antigens | Antibody titers were measured in geometric mean titers (GMTs), calculated on all subjects. | At pre-primary vaccination (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBAMenW-135 and hSBA-MenY Titers ≥ the Cut-off Values | The cut-off value for the assay was ≥ 1:4. | Pre-primary vaccinarion (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBAMenW-135 and hSBA-MenY Titers ≥ the Cut-off Values | The cut-off value for the assay ≥ 1:8. | Pre-primary vaccinarion (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Antibody Titers for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Meningococcal Antigens | Antibody titers were measured in Geometric mean titers (GMTs), calculated on all subjects. | Pre-primary vaccination at Month 0, post first vaccine dose at Month 1 and post second vaccine dose at Month 3 | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentrations ≥ the Cut-off Values | The cut-off value for the assay was ≥ 0.3 micrograms per milliliter (μg/m). | Pre-primary vaccinarion (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentration ≥ the Cut-off Values | The cut-off value for the assay was ≥ 2.0 μg/mL. | Pre-primary vaccinarion (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Antibody Titers for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Meningococcal Antigens | Antibody titers were measured in geometric mean concentrations (GMCs), calculated on all subjects. | Pre-primary vaccinarion (Month 0), post first vaccine dose (Month 1) and post second vaccine dose (Month 3) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms at Age Stratum 1-5 Years | 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. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms at Age Stratum 6-17 Years | Assessed solicited local symptoms were pain, redness and swelling. Any was defined as occurrence of the symptom regardless of intensity grade. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling spreading beyond 30 millimeters (mm) of injection site. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms at Age Stratum 1-5 Years | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptoms = symptoms which prevented normal everyday activities. Grade 3 fever = oral temperature >39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms at Age Stratum 6-17 Years | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever. Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptoms = symptoms which prevented normal everyday activities. Grade 3 fever = oral temperature >39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Days 0-3) post-vaccination period following each dose and across doses | 
| Number of Subjects Reporting New Onset of Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type 1 diabetes and allergies. | From Month 0 until the end of the Extended Safety Follow-Up [ESFU] (at Month 8) | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) | An unsolicited adverse event (AE) covers any untoward medical occurrence in a clinical subject investigation temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an AE reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. | During the 31-day (Days 0-30) post first vaccination period | 
| Number of Subjects Reporting Any Unsolicited AEs | An unsolicited AE covers any untoward medical occurrence in a clinical subject investigation temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an AE reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. | During the 31-day (Days 0-30) post second vaccination period | 
| 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. | From Month 0 until the end of the ESFU (at Month 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal vaccines, Vaccines, conjugate, Neisseria meningitidis, Immunocompromised patient