The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Toddlers

Study Overview
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Brief Summary
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In this study, the concentration of antibody to the vaccine one year, three and five years after vaccination in subjects who were vaccinated with GSK Biologicals' meningococcal vaccine GSK134612 in a previous study (whose objectives & outcome measures are presented in a separate protocol posting with NCT number =00471081) will be evaluated. The safety and immune response of a booster dose of vaccine GSK134612 administered at 5 years post-primary vaccination will also be evaluated. In addition, the immune response to a dose of vaccine GSK134612 administered to age-matched controls not previously given a meningococcal vaccine will be evaluated. This protocol posting has been updated further to protocol amendment 2, dated 28 october 2010. The sections impacted are summary, study design, outcome measures, intervention, and eligibility criteria.

Detailed Description
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GSK Biologicals has developed a meningococcal conjugate vaccine (GSK134612). This candidate vaccine has been shown to be well tolerated and immunogenic in toddlers. The purpose of this study is to evaluate the antibody persistence at approximately 1 year, 3 years and 5 years post-administration of one dose or two doses of GlaxoSmithKline (GSK) Biologicals' meningococcal vaccine GSK134612 when given to healthy toddlers 9-12 months of age. To evaluate, the safety and immunogenicity of a booster dose of GSK134612 administered to all eligible subjects at 5 years after the primary vaccination. To evaluate the safety and immunogenicity in a new group of subjects aged 5-6 years (naive control group) who will receive a single dose of vaccine GSK134612.

Official Title
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Long Term Antibody Persistence Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Administered as 1 or 2 Doses to Healthy Toddlers at 9-12 Months of Age and as a Booster Dose at 5 Years Post-primary Vaccination

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: All subjects must satisfy the following criteria for the persistence phase of the study entry: A male or female toddler who was vaccinated 1, 3 or 5 years ago with the last dose of MenACWY-TT in study with NCT number=00471081. Written informed consent obtained from parents/guardian of the subject. Healthy subjects as established by medical history before entering into the study. Having completed the active phase of the vaccination study with NCT number=00471081 (i.e., not withdrawn, had received all planned doses of study vaccines, provided a post-vaccination blood sample after the final dose). All subjects must meet the following criteria prior to receiving the booster vaccination: Written informed consent obtained from parents/guardian of the subject. Subjects who can and will comply with the requirements of the protocol. Subjects who provide a blood sample 5 years after last vaccination in study with NCT number=00471081. All subjects must satisfy the following criteria prior to enrollment in the naïve control group: Subjects who the investigator believes can and will comply with the requirements of the protocol. A male or female between, and including, 5-6 years of age at the time of the vaccination. Written informed consent obtained from parents/guardian of the subject. Healthy subjects as established by medical history and history-directed physical examination before entering into the study. Exclusion Criteria: Exclusion criteria for persistence study entry Use of any investigational or non-registered product (drug or vaccine) within 30 days of each persistence timepoint. Vaccination with meningococcal polysaccharide or conjugate vaccine of serogroup A, B, C, W-135, and/or Y outside of study with NCT number=00471081. History of any meningococcal disease due to serogroup A, B, C, W-135, or Y. Any confirmed or suspected immunosuppressive or immunodeficiency condition based on medical history and physical examination (no laboratory testing is required). Administration of immunoglobulins and/or any blood products within the three months preceding each persistence timepoint. Concurrently participating in another clinical study within 30 days of each persistence timepoint, 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. Subjects withdrew consent to be contacted for follow-up studies. Exclusion criteria for primary (naive control)/booster vaccination at year 5 study entry (to be checked at Year 5) Child in care. Subjects who were enrolled in the Kaiser Healthcare system in study with NCT number=00471081, but are no longer enrolled. Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the primary (naive control)/booster vaccination, 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 primary (naive control)/booster vaccination. (For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed). Vaccination with meningococcal polysaccharide or conjugate vaccine outside of study with NCT number=00471081. History of any meningococcal disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history (no laboratory testing is required). Administration of immunoglobulins and/or any blood products within the three months preceding the primary (naive control)/booster vaccination or planned administration during the study period. 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). Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy. Subjects withdrew consent to be contacted for follow-up studies. Hypersensitivity to latex. Previous administration or planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days of the study vaccination (primary vaccination for the naïve control group and booster vaccination for subjects primed in Study with NCT number = 00471081) and ending 30 days after with the exception of any licensed inactivated influenza vaccine (live attenuated influenza vaccine is not allowed). Previous administration or planned administration of tetanus or any tetanus containing vaccine during the period starting from 30 days of the study vaccination and ending 30 days after. A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Major congenital defects or serious chronic illness. History of any neurological disorders or seizures. Acute disease at the time of vaccination. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature by any method < 99.5°F (37.5°C).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 6 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects who were previously vaccinated with one dose of GSK134612 at 12 months of age. | Biological: Meningococcal vaccine GSK134612<br>* One dose, as intramuscular injection<br>|
| Experimental: Group B<br>Subjects who were previously vaccinated with two doses of GSK134612, one each at 9 and 12 months of age. | Biological: Meningococcal vaccine GSK134612<br>* One dose, as intramuscular injection<br>|
| Experimental: Group C<br>Subjects aged 5-6 years not previously administered meningococcal vaccine. | Biological: Meningococcal vaccine GSK134612<br>* One dose, as intramuscular injection<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 (Using Human Complement) (hSBA) Titers ≥ the Cut-off | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was greater than or equal to ( ≥) 1:8. | At Year 1 (12 months post primary vaccination) | 
| Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was ≥ 1:8. | At Year 3 (36 months post primnary vaccination) | 
| Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was ≥ 1:8. | At Year 5 (60 months post primary vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was ≥ 1:4. | At Year 1 (12 months post vaccination) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was ≥ 1:4. | At Year 3 (36 months post primary vaccination) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed was ≥ 1:4. | At Year 5 (60 months post primary vaccination) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBAMenW-135, and hSBA-MenY respectively, calculated on all subjects. | At Year 1 (12 months post primary vaccination) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBAMenW-135, and hSBA-MenY respectively, calculated on all subjects. | At Year 3 (36 months post primary vaccination) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBAMenW-135, and hSBA-MenY respectively, calculated on all subjects. | At Year 5 (60 months post primary vaccination) | 
| Number of Subjects With Titers ≥ the Cut-off for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed were ≥ 1:8 and 1:128. The analysis was performed by GSK Biologicals' laboratory assay. | At Year 1 (12 months post primary vaccination) | 
| Number of Subjects With Titers ≥ the Cut-off, for MenA , MenC, MenW-135 and MenY Serum Bactericidal Antibodies, Using Baby Rabbit Complement | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed were ≥ 1:8 and 1:128. The analysis was performed by GSK Biologicals' laboratory assay. | At Year 3 (36 months post primary vaccination) | 
| Number of Subjects With Titers ≥ the Cut-off for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off values assessed were ≥ 1:8 and 1:128. Titers were determined by Public Health England (PHE) laboratory assay. | At Year 3 (36 months post primary vaccination) | 
| Number of Subjects With Titers ≥ the Cut-off, for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off values assessed were ≥ 1:8 and 1:128. The analysis was performed by GSK Biologicals' laboratory assay. | At Year 5 (60 months post-primary vacccination). | 
| Number of Subjects With Titers ≥ the Cut-off for Men-A , Men-C, Men-W-135 and Men-Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off values assessed were ≥ 1:8 and 1:128 determined by Public Health England (PHE) laboratory assay. | At Year 5 (60 months post-primary vacccination) | 
| rSBA Antibody Titers | Titers were given as geometric mean titers (GMTs) for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively, as performed by GSK Biologicals' laboratory assay. | At Year 1 (12 months post primary vaccination) | 
| rSBA Antibody Titers. | Titers are given as geometric mean titers (GMTs) for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively, as performed by GSK Biologicals' laboratory assay. | At Year 3 (36 months post-primary vaccination) | 
| rSBA Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY respectively. Titers were determined by Public Health England (PHE) laboratory assay. | At Year 3 (36 months following primary vaccination) | 
| rSBA Antibody Titers | Titers are given as geometric mean titers (GMTs), calculated on all subjects for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively by GSK Biologicals' laboratory assay. | At Year 5 (60 months post-primary vacccination) | 
| rSBA Antibody Titers. | Titers are given as geometric mean titers (GMTs), calculated for all subjects for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively. Titers were determined by Public Health England (PHE) laboratory assay. | At Year 5 (60 months following primary vaccination) | 
| Antibody to Polysacccharide N. Meningitidis Serogroup A, C, W-135 and Y (Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY) Antibody Concentrations | Results were tabulated as geometric mean antibody concentration (GMC) calculated on all subjects, expressed in microgram per milliliter (μg/ml). | At Year 1 (12 months post primary vaccination) | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 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. | At Year 1 (12 months post primary vaccination) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers ≥ Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed were ≥ 1:4 or 1:8. This outcome measure only concerns the Nimenrix Naive Group. | At Month 60 (pre-primary vaccination with Nimenrix vaccine) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBAMenW-135, and hSBA-MenY respectively. This outcome measure only concerns the Nimenrix Naive Group. | At Month 60 (pre-vaccination with Nimenrix vaccine) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ Cut-off Values | rSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off value assessed were ≥ 1:8 or 1:128. This outcome measure only concerns the Nimenrix Naive Group. | At Month 60 (pre-primary vaccination with Nimenrix vaccine) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively. This outcome measure only concerns the Nimenrix Naive Group. | At Month 60 (pre-primary vaccination with Nimenrix vaccine) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers ≥ Cut-off Values | hSBA antibody titers were assessed for the MenA, MenC, MenW-135, and MenY serogroups respectively. The antibody cut-off values assessed were ≥ 1:4 or 1:8. | At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers | Titers were given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC,hSBAMenW-135, and hSBA-MenY respectively, calculated on all subjects. | At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| Number of Subjects With Vaccine Response for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers | Vaccine response was defines as: for initially seronegative subjects (pre-vaccination titer < 1:4): hSBA post-vaccination antibody titers ≥ 1:8 and for seropositive subjects (pre-vaccination titers ≥ 1:4): hSBA antibody titers at least four times the pre-vaccination antibody titers. | At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBAMenW-135 and rSBA-MenY Titers ≥ the Cut-off Values | The cut-off values for the assay were ≥1:8 and ≥1:128. Titers were determined by Public Health England (PHE) laboratory assay. | At Month 60 and 61 (just prior to and one month post-primary vaccination for Nimenrix Naive Group; one month post-booster vaccination for Nimenrix 1 and Nimenrix 2 Groups) | 
| rSBA Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups rSBA-MenA, rSBA-MenC, rSBAMenW-135, and rSBA-MenY respectively, determined by Public Health England [PHE] laboratory assay. | At Month 60 and 61 (just prior to and one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups) | 
| Number of Subjects With Vaccine Response With rSBA-MenA, rSBA-MenC, hSBA-MenW-135 and rSBA-MenY Antibody Titers | Vaccine response was defined as: for initially seronegative subjects: antibody titer ≥ 1:32 at post-vaccination; and for initially seropositive subjects: antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer. Titers were determined by Public Health England (PHE) laboratory assay. | At Month 61 (one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptom | 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 pain that prevented normal activity. Grade 3 redness/swelling was defined as redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 4-day (Days 0-3) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptom | Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache and gastrointestinal. Any was defined as occurrence of the symptom regardless of their intensity grade or relationship to study vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever higher than (>) 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Days 0-3) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| Number of Subjects Reporting 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. | During the 31-day (Days 0-30) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups | 
| 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. | During the 181-day (Days 0-180) post primary vaccination for Nimenrix Naive Group and post booster for Nimenrix 1 and Nimenrix 2 Groups | 
| Number of Subjects Reporting Any New Onset of Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | During the 181-day (Days 0-180) post primary vaccination for Nimenrix Naive Group and post booster for Nimenrix 1 and Nimenrix 2 Groups | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Vaccines, conjugate, Immunogenicity, Meningococcal vaccine, Booster vaccination, Primary vaccination, Neisseria meningitides, Toddlers, Humans, Meningococcal disease