The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Adolescents/Adults

Study Overview
=================
Brief Summary
-----------------
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 and Menactra® in a previous study (whose objectives & outcome measures are presented in a separate protocol posting with NCT number =00454909) will be evaluated. The safety and immune response to a booster dose of vaccine GSK134612 administered at 5 years post-primary vaccination and a primary vaccination of a newly enrolled group with GSK 134612 vaccine will also be evaluated.

Detailed Description
-----------------
GSK Biologicals has developed a meningococcal conjugate vaccine (GSK134612). This candidate vaccine has been shown to be well tolerated and immunogenic in subjects as of 12 months of age. 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 of GlaxoSmithKline (GSK) Biologicals' meningococcal vaccine GSK134612 as compared to Menactra® (meningococcal serogroups A, C, W-135 and Y-diphtheria toxoid conjugate vaccine, sanofi pasteur) when given to healthy adolescents/ adults 11 to 25 years of age In addition, the safety and immunogenicity of a booster dose of GSK134612 administered to all eligible subjects at 5 years after the primary vaccination will be evaluated. Another cohort of subjects (naïve control group) 15 to <31 years of age will be offered a dose of MenACWY-TT vaccine at the same time to allow for evaluation of a primary (naïve control group) and booster dose within the same study. This Protocol Posting has been updated following Protocol Amendment 1, May 2010 and Protocol Amendment 2, May 2011.

Official Title
-----------------
Long-term Antibody Persistence of GSK Biologicals' MenACWY-TT Vaccine Versus Menactra® in Healthy Adolescents/Adults Aged 10-25 Years and Booster Response to MenACWY-TT Vaccine Administered at 5 Years Post-primary Vaccination

Conditions
-----------------
Infections, Meningococcal

Intervention / Treatment
-----------------
* Biological: Nimenrix
* Procedure: Blood sampling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Persistence phase: A male or female who was between and including 10 and 25 years of age at the time of primary vaccination in the study with NCT number = 00454909. Written informed consent obtained from parents/guardian of the subject and written informed assent obtained from the subject if the subject is less than 18 years of age, or written informed consent obtained from the subject if the subject has achieved the 18th birthday. Healthy subjects as established by medical history. Having completed the active phase of the vaccination study with NCT number = 00454909. Booster phase: Written informed consent obtained from parents/guardian of the subject and written informed assent obtained from the subject if the subject is less than 18 years of age, or written informed consent obtained from the subject if the subject has achieved the 18th birthday. Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. Healthy subjects as established by medical history and history-directed physical examination before entering into the study. If the subject is female, she must be of non-childbearing potential, i.e., pre-menarche, have a current tubal ligation, hysterectomy, oophorectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test on the day of vaccination and continue adequate contraception for 2 months after vaccination. Additional inclusion criterion for the naïve control group: • A male or female between, and including, 15 and 30 years of age at the time of the vaccination. Exclusion Criteria: Persistence phase: Use of any investigational or non-registered product within 30 days of each persistence time point. Vaccination with meningococcal polysaccharide or conjugate vaccine of serogroup A, C, W-135, and/or Y outside of study with NCT number = 00454909. History of any meningococcal disease due to serogroup A, B, C, W-135, or Y. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history. Administration of immunoglobulins and/or any blood products within the three months preceding each persistence time point. Concurrently participating in another clinical study within 30 days of each persistence time point, in which the subject has been or will be exposed to an investigational or a non-investigational product. Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy. Chronic alcohol or drug abuse. Subjects withdrew consent to be contacted for follow-up studies. Booster phase (to be checked at Year 5 for all subject, including naïve control group): Child in care Not enrolled in the Kaiser Healthcare system. Use of any investigational or non-registered product within 30 days preceding administration of the study vaccine, or planned use throughout the extended safety follow-up period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior administration of the booster dose. Previous vaccination with meningococcal polysaccharide or conjugate vaccine of serogroup A, C, W-135, and/or Y outside of study with NCT number = 00454909. History of any meningococcal disease. Any confirmed or suspected immunosuppressive or immunodeficient condition,including human immunodeficiency virus infection based on medical history and physical examination. Administration of immunoglobulins and/or any blood products within the three months preceding the booster vaccination or planned administration through Day 30 after vaccination. 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. Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy. History of chronic alcohol consumption and/or drug abuse. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before until 30 days after the day of administration of the dose of vaccine(s) with the exception of any licensed inactivated influenza vaccine. Previous vaccination with tetanus and diphtheria toxoids within the last month. A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated. History of allergic disease or any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine, including latex. Major congenital defects or serious chronic illness. History of any neurological disorders or seizures. Previous history of Guillain-Barré syndrome Acute disease at the time of vaccination. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months after vaccination. For groups A, B and C only: Subjects withdrew consent to be contacted for follow-up studies. Note: if the subject is female, prior to vaccination she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test on the day of vaccination and continue adequate contraception for 2 months after vaccination.

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimenrix 1 Group<br>Subjects 11-25 years of age who were previously vaccinated with 1 dose of Nimenrix vaccine at the time of vaccination | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);Procedure: Blood sampling<br>* Blood samples will be collected from subjects 10-25 years of age as per enrollment in primary study and from subjects in the Nimerix Naive Group at Month 60 (Year 5) and 1 month post booster vaccination (Month 61).<br>|
| Active Comparator: Menactra Group<br>Subjects 11-25 years of age who were previously vaccinated with 1 dose of Menactra vaccine at the time of vaccination | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);Procedure: Blood sampling<br>* Blood samples will be collected from subjects 10-25 years of age as per enrollment in primary study and from subjects in the Nimerix Naive Group at Month 60 (Year 5) and 1 month post booster vaccination (Month 61).<br>|
| Experimental: Nimenrix 2 Group<br>Subjects 10<11 years of age who were previously vaccinated with 1 dose of Nimenrix vaccine at the time of vaccination | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);Procedure: Blood sampling<br>* Blood samples will be collected from subjects 10-25 years of age as per enrollment in primary study and from subjects in the Nimerix Naive Group at Month 60 (Year 5) and 1 month post booster vaccination (Month 61).<br>|
| Experimental: Nimenrix Naive Group<br>Subjects 15 to <31 years of age at the time of primary vaccination with 1 dose of Nimenrix vaccine at year 5 of the current study | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);Procedure: Blood sampling<br>* Blood samples will be collected from subjects 10-25 years of age as per enrollment in primary study and from subjects in the Nimerix Naive Group at Month 60 (Year 5) and 1 month post booster vaccination (Month 61).<br>|
| Experimental: Nimenrix Pooled Group<br>Pooled group of subjects 10-25 years of age from Nimenrix 1 and Nimenrix 2 groups in the primary study (NCT00454909) who had received 1 dose of Nimenrix vaccine in that study and will receive a booster dose in this current study. | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);|
| Active Comparator: Menactra Booster Group<br>Subjects 11-25 years of age who had received 1 dose of Menactra vaccine in primary study (NCT00454909) and will receive 1 dose of Nimenrix vaccine in this current study. | Biological: Nimenrix<br>* One dose, as intramuscular injection<br>* Other names: Meningococcal vaccine GSK134612 (MenACWY-TT);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:8. | At year 1 persistence | 
| Number of Subjects With hSBA Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:8. | At year 3 persistence | 
| Number of Subjects With hSBA Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:8. | At year 5 persistence | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With hSBA Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:4. | At year 1 persistence | 
| Number of Subjects With hSBA Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:4. | At year 3 persistence | 
| Number of Subjects With hSBA Titers Equal to or Above the Cut-off Values | hSBA antibody titers were assessed for the hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY serogroups respectively. The antibody cut-off value assessed was equal to or above 1:4. | At year 5 persistence | 
| hSBA Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY respectively. | At year 1 persistence | 
| hSBA Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY respectively. | At year 3 persistence | 
| hSBA Antibody Titers | Titers are given as geometric mean titers (GMTs) for the serogroups hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY respectively. | At year 5 persistence | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSY, and Anti-PSW-135 Concentrations Equal to or Above the Cut-off Values | The cut-off values were defined as a concentration ≥0.3 microgram per milliliter (μg/mL) and ≥2.0 μg/mL. | At year 1 persistence | 
| Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSY, and Anti-PSW-135 Antibody Concentrations | Antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in μg/mL. | At year 1 persistence | 
| Number of Subjects With Serious Adverse Events (SAEs) Related to a Concurrent GSK Medication | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From 6 months up to 1 year following primary vaccination | 
| Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From 6 months up to 3 years following primary vaccination | 
| Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | From 6 months up to 5 years following primary vaccination | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Equal to or Above the Cut-off Values | The cut-off values were defined as hSBA antibody titers ≥ 1:4 and ≥ 1:8. | 1 month post primary (naïve control group) and booster vaccination | 
| hSBA Antibody Titers | Titers are given as GMTs for the serogroups hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY respectively. | 1 month post primary (naïve control group) and booster vaccination | 
| Number of Subjects With Vaccine Response for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibodies | Vaccine response was defined as: For initially seronegative subjects: antibody titre ≥ 1:8 at one month after vaccination For initially seropositive subjects: antibody titre at one month after vaccination ≥ 4 fold the titres before vaccination. | 1 month post primary (naïve control group) and booster vaccination | 
| Number of Subjects With Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of any solicited local symptom reported irrespective of intensity grade. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 50 millimeter (mm). | During the 4-day (Days 0-3) post primary (naïve control group) and booster vaccination | 
| Number of Subjects With Solicited General Symptoms | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhea and/or abdominal pain), headache and temperature. Any = occurrence of any general symptoms reported irrespective of intensity grade and relationship to study vaccination. Any temperature = axillary temperature greater than or equal to (≥)37.5 degrees Celsius (°C). Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 temperature = axillary temperature above 39.0°C. Related = symptoms considered by the investigator to have a causal relationship to vaccination. | During the 4-day (Days 0-3) post primary (naïve control group) and booster vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | Unsolicited AE covers any AE 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. | During the 31-day (Days 0-30) following primary (naïve control group) and booster vaccination | 
| Number of Subjects Reporting New Onset Chronic Illness(es) (NOCIs) | Examples of NOCIs include autoimmune disorders, asthma, type 1 diabetes and allergies. | During the 6-month period following the primary (naïve control group) and booster vaccination | 
| Number of Subjects With SAEs | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | During the 6-month period following the primary (naïve control group) and booster vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Meningococcal vaccine, Booster vaccination, Immunogenicity, Meningococcal disease, Safety