Study to Evaluate the Long-term Antibody Persistence of GlaxoSmithKline (GSK) Biologicals' MenACWY-TT Vaccine (GSK134612) Versus Mencevax ACWY in Healthy Adolescents and Adults and Booster Response to MenACWY-TT Vaccine Administered at 10 Years Post-primary Vaccination

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term antibody persistence from 6, 7, 8, 9 to 10 years post-administration of MenACWY-TT conjugate vaccine as compared to Mencevax ACWY when given to healthy subjects 11 to 55 years of age. In addition, the safety and immunogenicity of a booster dose of MenACWY-TT vaccine administered to all eligible subjects 10 years after the primary vaccination will be evaluated. All Filipino subjects who received the primary vaccination in the primary vaccination study 107386 (NCT00356369) will be invited to enrol in the long-term follow up and booster phase. No new subjects will be enrolled.

Official Title
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A PHASE IIIB, OPEN, MULTI-CENTER STUDY TO EVALUATE THE LONG-TERM ANTIBODY PERSISTENCE AT 6, 7, 8, 9 AND 10 YEARS AFTER THE ADMINISTRATION OF ONE DOSE OF MENINGOCOCCAL CONJUGATE VACCINE MENACWY-TT VERSUS ONE DOSE OF MENINGOCOCCAL POLYSACCHARIDE VACCINE MENCEVAX(REGISTERED) ACWY, AND TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A BOOSTER DOSE OF MENACWY-TT VACCINE ADMINISTERED 10 YEARS AFTER PRIMARY VACCINATION OF 11-55 YEAR OLD SUBJECTS WITH MENACWY-TT OR MENCEVAX (REGISTERED) ACWY.

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 at study entry to the persistence phase: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Or /and subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female between and including 17 and 66 years of age at the time of entry into the present study. Has completed the vaccination phase of the vaccination study MENACWY-TT-015. In alignment with local laws and regulations, written informed consent obtained from parents/LAR(s) 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. The subjects ≥18 years of age at the time of enrollment will sign the informed consent form, even if the parent/ LAR previously signed the ICF before the subject reached the legal age of consent. Healthy subjects as established by medical history and history-directed physical examination before entering into the study. All subjects must satisfy the following additional criteria prior to entry of the booster phase: Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Child in care. Previous vaccination with meningococcal polysaccharide or conjugate vaccine outside of study MENACWY-TT-015. History of meningococcal disease due to serogroup A, C, W-135 or Y. Any confirmed or suspected immunosuppressive or immunodeficient condition, including Human Immunodeficiency Virus (HIV) infection, based on medical history and physical examination. Major congenital defects or serious chronic illness. Family history of congenital or hereditary immunodeficiency. History of chronic alcohol consumption and/or drug abuse. Additional exclusion criteria for booster phase at Month 120 study entry (to be checked at Month 120) for all subjects Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the booster dose of study vaccine, or planned use during the follow-up period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose. Inhaled and topical steroids are allowed. Administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the booster dose of study vaccine or planned administration within 30 days after vaccination (with the day of vaccination considered Day 0), with the exception of a licensed inactivated influenza vaccine. Administration of immunoglobulins and/or any blood products within the three months preceding the booster vaccination or planned administration during the follow-up 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 vaccine/product. Previous vaccination with tetanus toxoids within the last month. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. 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 enrollment. Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C for rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 66 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: ACWY-TT group<br>All subjects vaccinated with MenACWY-TT in study MENACWY-TT-015 will be assigned to this group. At Month 120 after primary vaccination, these subjects will be vaccinated with a booster dose of MenACWY-TT in this study. | Biological: Meningococcal vaccine GSK134612<br>* 1 dose administered intramuscularly in the non-dominant deltoid region.<br>|
| Active Comparator: MenPS group<br>All subjects vaccinated with Mencevax ACWY in study MENACWY-TT-015 will be assigned to this group. At Month 120 after primary vaccination, these subjects will be vaccinated with a dose of MenACWY-TT in this study. | Biological: Meningococcal vaccine GSK134612<br>* 1 dose administered intramuscularly in the non-dominant deltoid region.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence Phase: Percentage of Participants With Serum Bactericidal Assay Using Rabbit Complement (rSBA) Titers Greater Than or Equal to (>=) 1:8 and >=1:128 For Each of the 4 Serogroups After 6 Years of Primary Vaccination | Serogroups included neisseria meningitidis serogroup A (MenA), Neisseria meningitidis serogroup C (MenC), Neisseria meningitidis serogroup W-135 (MenW-135) and Neisseria meningitidis serogroup Y (MenY). | After 6 years of primary vaccination | 
| Persistence Phase: Percentage of Participants With rSBA Titers >= 1:8 and >=1:128 For Each of the 4 Serogroups After 7 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | After 7 years of primary vaccination | 
| Persistence Phase: Percentage of Participants With rSBA Titers >= 1:8 and >=1:128 For Each of the 4 Serogroups After 8 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | After 8 years of primary vaccination | 
| Persistence Phase: Percentage of Participants With rSBA Titers >= 1:8 and >=1:128 For Each of the 4 Serogroups After 9 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | After 9 years of primary vaccination | 
| Persistence Phase: Percentage of Participants With rSBA Titers >= 1:8 and >=1:128 For Each of the 4 Serogroups After 10 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | After 10 years of primary vaccination | 
| Persistence Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups After 6 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 percentage (%) reduction of meningococcal colony-forming units. | After 6 years of primary vaccination | 
| Persistence Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups After 7 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 % reduction of meningococcal colony-forming units. | After 7 years of primary vaccination | 
| Persistence Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups After 8 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 % reduction of meningococcal colony-forming units. | After 8 years of primary vaccination | 
| Persistence Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups After 9 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 % reduction of meningococcal colony-forming units. | After 9 years of primary vaccination | 
| Persistence Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups After 10 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 % reduction of meningococcal colony-forming units. | After 10 years of primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Booster Phase: Percentage of Participants With rSBA Titers >=1:8 and >=1:128 For Each of the 4 Serogroups at 1 Month After Booster Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 1 month after booster vaccination | 
| Booster Phase: Geometric Mean Titers With rSBA for Each of the 4 Serogroups at 1 Month After Booster Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA titers expressed as the reciprocal of the highest serum last dilution resulting in at least 50 % reduction of meningococcal colony-forming units. | 1 month after booster vaccination | 
| Booster Phase: Percentage of Participants With rSBA Booster Response at 1 Month After Booster Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. rSBA booster vaccine responses for serogroups A, C, W-135 and Y defined as: for initially seronegative participants (pre-vaccination titer below the cut-off of 1:8) had rSBA antibody titers >= 1:32, 1 month after vaccination, and for initially seropositive participants (pre-vaccination titer >= 1:8) had rSBA antibody titers at least 4 times the pre-vaccination antibody titers, 1 month after vaccination. Data reported below is including both seropositive and seronegative participants. | 1 month after booster vaccination | 
| Booster Phase: Percentage of Participants With Antibodies Against-Tetanus Toxoid (Anti-TT) Concentrations >=0.1 International Units Per Millilitre (IU/mL), >=1.0 IU/mL at 1 Month After Booster Vaccination | Tetanus toxoid (TT) was used as carrier in tetravalent meningococcal ACWY conjugate vaccine. Percentage of participants with anti-TT concentration >=0.1 IU/mL, >=1.0 IU/mL were summarized. | 1 month after booster vaccination | 
| Booster Phase: Geometric Mean Concentrations (GMCs) of Antibodies Against-Tetanus Toxoid (Anti-TT) at 1 Month After Booster Vaccination | TT was used as carrier in tetravalent meningococcal ACWY conjugate vaccine. Percentage of participants with anti-TT concentration >=0.1 IU/mL, >=1.0 IU/mL were summarized. | 1 month after booster vaccination | 
| Booster Phase: Percentage of Participants With Solicited Local and General Adverse Events up to 4 Days Post Booster Vaccination | Solicited local events:1)pain(Grade [G] : 0=none,1=mild,neither interfered nor prevented normal activities,2=moderate, painful when limb moved; interfered with normal activities,3=severe, significant pain at rest,prevented normal activities),2)redness, and 3)swelling (record greatest surface diameter in millimetre[mm] as 0 to less than or equal to[<=]20 mm, greater than[>]20 to <=50 mm,>50 mm). If to resolve any event medical advice taken, results reported as Medical Advice. Solicited general events: 1) fatigue, 2) gastrointestinal(GI) events(nausea, vomiting, diarrhea and/or abdominal pain,3) headache(G : 0=normal, 1=mild, easily tolerated,2=moderate, interfered with normal activity,3=severe, prevented normal activity), and 4)fever (G: 0=less than[<] 37.5 degree Celsius[°C], 1= 37.5 degree C to 38.0degree C, 2= 38.1 degreeC to 39.0 degree C,3 =>39.0 degree C). 'Related'=relationship to study vaccine assessed by investigator.Medical advice=medical advice received to resolve any event. | Up to 4 days post booster vaccination | 
| Booster Phase: Percentage of Participants With Unsolicited Adverse Events (AEs) up to 31 Days Post Booster Vaccination | An AE was any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE covers any untoward medical occurrence in a clinical investigation participant 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. | Up to 31 days post booster vaccination | 
| Booster Phase: Percentage of Participants With Serious Adverse Events (SAEs) From Booster Vaccination up to End of Study (6 Months Post Booster Vaccination) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to 6 months post booster vaccination | 
| Booster Phase: Percentage of Participants With New Onset Chronic Illness From Booster Vaccination up to End of Study (6 Months Post Booster Vaccination) | New onset chronic illness included autoimmune disorders, asthma, type I diabetes, and allergies. | Up to 6 months post booster vaccination | 
| Booster Phase: Percentage of Participants With Guillain-Barre Syndrome (GBS) From Booster Vaccination up to End of Study (6 Months Post Booster Vaccination) | Guillain-Barre syndrome (GBS) is a rare neurological disorder in which the body's immune system mistakenly attacks part of its peripheral nervous system-the network of nerves located outside of the brain and spinal cord. GBS can range from a very mild case with brief weakness to nearly devastating paralysis, leaving the person unable to breathe independently. | Up to 6 months post booster vaccination | 
| Booster Phase: Percentage of Participants With Meningococcal Disease From Booster Vaccination up to End of Study (6 Months Post Booster Vaccination) | Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also termed meningococcus). It causes two life threatening diseases: meningococcal meningitis and fulminant meningococcemia which often occur together. Meningococcal meningitis is defined as an inflammatory response to bacterial infection of leptomeninges (pia-arachnoid) and the sub-arachnoid space. Meningococcal meningococcemia is meningococcal septicemia when the bacteria circulate and multiply in blood and involve multiple organs. It can cause multi-organ failure and severe disability or death. | Up to 6 months post booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Adults, Safety, Neisseria meningitidis, Booster response, Immunogenicity, Adolescents, Serogroups A, C, W-135, and Y, long-term antibody persistence