The Long-term Antibody Persistence of MenACWY-TT Vaccine (PF-06866681) Versus Meningitec(Registered) or Mencevax(Registered) ACWY in Healthy Adolescents and Adults and a Booster Dose of MenACWY-TT Administered 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 6, 7, 8, 9 and 10 years after receiving a primary vaccination of meningococcal conjugate vaccine MenACWY-TT versus Meningitec™ or Mencevax™ ACWY, and the safety and immunogenicity of a booster dose of MenACWY-TT administered 10 years after the primary vaccination. All subjects received a primary vaccination at 1 to 10 years of age in study 108658 (NCT00427908). No new subjects will be enrolled in this booster study.

Detailed Description
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The study aims to evaluate the antibody persistence post primary vaccination with active control, safety and immunogenicity of a booster dose uncontrolled post primary vaccination during different phases: Persistence phase: Long-term persistence 6, 7, 8, 9 and 10 years after primary vaccination with MenACWY-TT or Meningitec or Mencevax ACWY, in study MenACWY-TT-027. Booster phase: One month post booster vaccination with MenACWY-TT vaccine ten years after primary vaccination. The subjects in this study will be allocated to the same groups as in the vaccination study MenACWY-TT-027 (NCT00427908).

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 THE MENINGOCOCCAL CONJUGATE VACCINE MENACWY-TT VERSUS ONE DOSE OF MENINGITEC(REGISTERED) VACCINE OR ONE DOSE OF THE 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 1-10 YEAR OLD SUBJECTS WITH MENACWY-TT, MENINGITEC(REGISTERED) 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: Subjects and/or subjects' parent(s)/Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female who has received a primary vaccination with the MenACWY-TT, Meningitec or Mencevax ACWY vaccines in study MenACWY-TT-027 (NCT00427908). 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 15 years of age, or written informed consent obtained from the subject if the subject has achieved the 15th birthday. The subjects ≥15 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, hysterectomy or bilateral ovariectomy. Male subjects able to father children and female subjects of childbearing potential (including females who have had tubal ligation) and at risk of pregnancy 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 (for females only), and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination. Exclusion Criteria: Child in care. Previous vaccination with meningococcal polysaccharide or conjugate vaccine outside of study MenACWY-TT-027. Note: Subjects who were revaccinated with a monovalent MenC conjugate vaccine because of suboptimal response during the persistence phase of the MenACWY-TT-027 study (i.e. MenACWY-TT-028, -029, -030, -031 and -032) are allowed to participate as they will be followed for the persistence of MenA, MenW-135 and MenY. History of meningococcal disease due to serogroup A, C, W-135 or Y. Previous vaccination with meningococcal B vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including Human Immunodeficiency Virus (HIV) infection, based on medical history and physical examination (no laboratory testing required). Family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. History of chronic alcohol consumption and/or drug abuse. Subjects who withdrew consent to be contacted for follow-up studies. Additional exclusion criteria for booster phase at Month 126 study entry (to be checked at Month 126) for all subjects: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the booster dose of study vaccine, or planned use during the follow-up period. 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 exception of a licensed inactivated influenza vaccine. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose . Inhaled and topical steroids are allowed. 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 . 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 vaccination. Fever is defined as temperature ≥ 37.5°C for oral, axillary, tympanic, or ≥38.0°C for rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) 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. Male subjects able to father children who are planning to discontinue contraceptive precautions. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
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: ACWY<2 Group<br>Subjects will receive a dose of MenACWY-TT 10 years after primary vaccination with MenACWY-TT. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the non-dominant arm<br>|
| Experimental: ACWY≥2 Group<br>Subjects will receive a dose of MenACWY-TT 10 years after primary vaccination with MenACWY-TT. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the non-dominant arm<br>|
| Experimental: MenCCRM Group<br>Subjects will receive a dose of MenACWY-TT 10 years after primary vaccination with Meningitec. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the non-dominant arm<br>|
| Experimental: MenPS Group<br>Subjects will receive a dose of MenACWY-TT 10 years after primary vaccination with Mencevax ACWY. | Biological: Meningococcal vaccine GSK134612<br>* One dose administered intramuscularly (IM) in the deltoid of the non-dominant arm<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 >=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). | 6 years after primary vaccination (Year 1 of study MENACWY-TT-100) | 
| 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. | 7 years after primary vaccination (Year 2 of study MENACWY-TT-100) | 
| 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. | 8 years after primary vaccination (Year 3 of study MENACWY-TT-100) | 
| 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. | 9 years after primary vaccination (Year 4 of study MENACWY-TT-100) | 
| 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. | 10 years after primary vaccination (Year 4 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by rSBA for Each of the 4 Serogroups After 6 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 6 Years after primary vaccination (Year 1 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by rSBA for Each of the 4 Serogroups After 7 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 7 years after primary vaccination (Year 2 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by rSBA for Each of the 4 Serogroups After 8 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 8 years after primary vaccination (Year 3 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by rSBA for Each of the 4 Serogroups After 9 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 9 years after primary vaccination (Year 4 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by rSBA for Each of the 4 Serogroups After 10 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 10 years after primary vaccination (Year 5 of study MENACWY-TT-100) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence Phase: Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >=1:4 and >=1:8 for Each of the 4 Serogroups After 6, 7, 8, 9 and 10 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 6, 7, 8, 9 and 10 years after primary vaccination (Year 1, 2, 3, 4 and 5 of study MENACWY-TT-100) | 
| Persistence Phase: Geometric Mean Titers as Measured by hSBA for Each of the 4 Serogroups After 6, 7, 8, 9 and 10 Years of Primary Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 6, 7, 8, 9 and 10 years after primary vaccination (Year 1, 2, 3, 4 and 5 of study MENACWY-TT-100) | 
| 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 (approximately Year 5.5 of study MENACWY-TT-100) | 
| Booster Phase: Geometric Mean Titers as Measured by rSBA For Each of the 4 Serogroups 1 Month After Booster Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. | 1 month after booster vaccination (approximately Year 5.5 of study MENACWY-TT-100) | 
| 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 response to meningococcal antigens (A,C, W-135 and Y) is defined as: rSBA antibody titer >= 1:32 one month after vaccination, and at least 4-fold increase in rSBA titers one month after vaccination. | 1 month after booster vaccination (approximately Year 5.5 of study MENACWY-TT-100) | 
| Booster Phase: Percentage of Participants With hSBA Titers >=1:4 and >=1:8 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 (approximately Year 5.5 of study MENACWY-TT-100) | 
| Booster Phase: Geometric Mean Titers Using hSBA 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 (approximately Year 5.5 of study MENACWY-TT-100) | 
| Booster Phase: Percentage of Participants With hSBA Booster Response at 1 Month After Booster Vaccination | Serogroups included MenA, MenC, MenW-135 and MenY. hSBA booster response to meningococcal antigens (A,C, W-135 and Y) is defined as: hSBA antibody titer >= 1:8 one month after vaccination, and at least 4-fold increase in hSBA titers one month after vaccination. | 1 month after booster vaccination (approximately Year 5.5 of study MENACWY-TT-100) | 
| Persistence Phase: Percentage of Participants With Serious Adverse Events (SAEs) Related to Vaccination or Any Adverse Event (AE) Related to Lack of Vaccine Efficacy | 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. AEs related to lack of vaccine efficacy were as judged by the investigator. | Through 5 years (6, 7, 8, 9 and 10 years post primary vaccination) | 
| Booster Phase: Percentage of Participants With Solicited Local and General Adverse Events up to 4 Days Post Booster Vaccination | Solicited general events: fatigue, gastrointestinal (GI) events (nausea, vomiting, diarrhea and/or abdominal pain, headache (0= normal, 1=mild/easily tolerated, 2=moderate/interfered with normal activity, 3=severe/prevented normal activity) and fever (>=37.5°C for oral/axillary/tympanic route, >=38.0°C for rectal route). Solicited local events: pain (0=none, 1=mild, not interfered/prevented normal activity, 2=moderate, painful when limb moved/interfered with normal activity, 3=severe, significant pain at rest/prevented normal activity), redness and swelling at injection site (record greatest surface diameter in millimeter (mm) as 0 to <=20 mm, >20 to <=50 mm, >50 mm). Participants may be represented in more than 1 category. Only categories with at least 1 participant reported. 'Medical advice' signifies medical advice received to resolve any event. 'Related'=relationship to study vaccine assessed by investigator. | Up to 4 days post booster vaccination | 
| Booster Phase: Percentage of Participants With Unsolicited Adverse Events 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) Up to 6 Months 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. 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 Up to 6 Months Post Booster Vaccination | New onset chronic illness included autoimmune disorders, asthma, type I diabetes, allergies. | 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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10 years Meningitec, Safety, booster response, Adolescents, Adults, Immunogenicity, Mencevax ACWY