Study in Adolescents/Adults to Evaluate Non-inferiority&Persistence up to 5 Years of GSK Bio MenACWY Conjugate Vaccine

Study Overview
=================
Brief Summary
-----------------
Meningococcal disease is mostly caused by N. meningitidis of serogroups A, B, C, W-135, Y. Meningococcal polysaccharide-conjugate vaccines have the advantage to induce a T-cell dependant immune response while the existing polysaccharide vaccines induce a T-cell independent response, i.e. with no immune memory response. GSK Biologicals has developed a combined Men ACWY conjugate vaccine intended to protect against meningococcal disease due to serogroups A, C, W-135 and Y. In the vaccination phase of this study, the new MenACWY-TT conjugate vaccine will be evaluated in adolescents and adults using Mencevax™ ACWY as control. In the long-term follow-up phase (extension phase) of the study, the long-term protection offered by the new MenACWY-TT conjugate vaccine will be assessed up to five years after the vaccination in adolescents and adults using Mencevax™ ACWY as control. This protocol posting deals with objectives & outcome measures of both the primary & extension phases.

Detailed Description
-----------------
All subjects will have 7 blood samples taken: prior to and one month after vaccination and one, two, three, four and five years after vaccination. No new subjects will be enrolled in the extension phases of this Phase IIb study. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

Official Title
-----------------
Phase IIb Primary Vaccination Study to Evaluate Non-Inferiority & Persistence of the Immune Response of GSK Biologicals' MenACWY Conjugate Vaccine (Intramuscularly) vs Mencevax ACWY (Subcutaneously) to Healthy Subjects (11-55 Years of Age)

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

Intervention / Treatment
-----------------
* Biological: meningococcal ACWY (vaccine)
* Biological: Mencevax™ ACWY


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes that they and/or their parents/ legally acceptable representative can and will comply with the requirements of the protocol. A male or female between, and including, 11 and 55 years of age at the time of vaccination. Written informed consent obtained from the subject/ from the parent or legally acceptable representative of the subject. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Previously completed routine childhood vaccinations to the best of his/her knowledge and/or his/her parents/legally acceptable representative's knowledge. If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, and must agree to continue such precautions for two months after completion of the vaccination series. Female subjects in childbearing potential who are not abstinent must have a negative pregnancy test. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, 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 vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine(s). Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C W and/or Y within the last five previous years. Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C W and/or Y. History of meningococcal disease due to serogroup A, C, W or Y. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. A family history of congenital or hereditary immunodeficiency. 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 neurologic disorders or seizures. History of Guillain-Barré syndrome. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. Pregnant or lactating female. History of chronic alcohol consumption and/or drug abuse. Female planning to become pregnant or planning to discontinue contraceptive precautions. Specific criteria to be checked at each study visit for the long term follow-up: History of meningococcal serogroup A,C, W and Y disease. Administration of a meningococcal polysaccharide or a meningococcal polysaccharide conjugate vaccine not planned in the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 11 Years
Maximum Age: 55 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 Group<br>Subjects receiving GSK Biologicals' meningococcal vaccine 134612 | Biological: meningococcal ACWY (vaccine)<br>* One intramuscular dose.<br>|
| Active Comparator: Mencevax Group<br>Subjects receiving Mencevax™ ACWY | Biological: Mencevax™ ACWY<br>* One subcutaneous dose.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine Response to Meningococcal Antigens for Serum Bactericidal Assay Using Rabbit Complement (rSBA) | Response to vaccine antigen was defined as: for initially seronegative subjects [subjects with serum bactericidal assay using rabbit complement (rSBA) titer lower than (<) 1:8, post-vaccination rSBA titer greater than or equal to (≥) 1:32] and for initially seropositive (subjects with rSBA titer ≥ 1:8), at least 4-fold increase in rSBA titer from pre to post vaccination. | One month post vaccination | 
| Occurrence of Any Grade 3 Systemic Symptoms | Local symptom, Grade 3 = pain that prevented normal activity and redness/ swelling spreading beyond (>) 50 millimeters (mm). General symptom, Grade 3 = symptom that prevented normal activity and fever (orally) >39.5 °C. | During the 4-day (Days 0-3) post-vaccination period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitidis Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and (≥) 1:128. | Prior to and 1 Month after vaccination | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | Prior to and 1 Month after vaccination | 
| Number of Subjects With Anti-Polysaccharide (Anti-PS) Antibodies | The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 micrograms per milliliter (μg/mL) and ≥ 2.0 μg/mL. | Prior to and 1 Month after vaccination | 
| Concentration of Anti-PS Antibodies | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in micrograms/milliliter (µg/mL). | Prior to and 1 Month after vaccination | 
| Number of Subjects With Anti-Tetanus (Anti-TT) Antibodies | Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). | Prior to and 1 Month after vaccination | 
| Concentration of Anti-TT Antibodies | Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL). | Prior to and 1 Month after vaccination | 
| Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titres was greater than or equal to (≥) 1:8 and ≥ 1:128. | At Year 1 | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | At Year 1 | 
| Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128. | At Year 2 | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | At Year 2 | 
| Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128. | At Year 3 | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | At Year 3 | 
| Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128. | At Year 4 | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | At Year 4 | 
| Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8 and ≥ 1:128. | At Year 5 | 
| rSBA Antibody Titers | Antibody titers are presented as Geometric Mean Titers (GMTs). | At Year 5 | 
| Number of Subjects With Anti-PS Antibodies | The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 μg/mL and ≥ 2.0 μg/mL. | At Year 1 | 
| Concentration of Anti-PS Antibodies | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL. | At Year 1 | 
| Number of Subjects With Anti-PS Antibodies | The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 μg/mL and ≥ 2.0 μg/mL. | At Year 2 | 
| Concentration of Anti-PS Antibodies | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL. | At Year 2 | 
| Number of Subjects With Anti-PS Antibodies | The cut-off value for the anti-PS concentration was greater than or equal to (≥) 0.3 micrograms per milliliter (μg/mL) and ≥ 2.0 μg/mL. | At Year 3 | 
| Concentration of Anti-PS Antibodies | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in µg/mL. | At Year 3 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Pain = pain that prevented normal activity. Grade 3 Redness/Swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With New Onset of Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | From Day 0 up to 6 Months after vaccination | 
| Number of Subjects With Rash |  | From Day 0 up to 6 Months after vaccination | 
| Number of Subjects With AEs Resulting in Emergency Rooms Visits |  | From Day 0 up to 6 Months after vaccination | 
| Number of Subjects With Unsolicited 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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | Up to 31 Days after vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Day 0 up to 6 Months after vaccination | 
| Number of Subjects With SAEs | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | At Year 1, Year 2, Year 3, Year 4 and Year 5 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunogenicity, Healthy, Persistence, Meningococcal vaccine, Non-inferiority, Meningococcal A C W Y Diseases, meningococcal serogroups A, C, W & Y diseases