Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Versus Mencevax™ ACWY in Healthy 18-25 Year Olds

Study Overview
=================
Brief Summary
-----------------
The purpose of the observer-blinded study is to determine the immunogenicity and safety of one dose of GlaxoSmithKline (GSK) Biologicals' meningococcal vaccine GSK 134612 compared to one dose of Mencevax™ ACWY in healthy subjects 18-25 years of age. In addition, this study will compare the immunogenicity of two lots of GSK's 134612 vaccine.

Official Title
-----------------
Immunogenicity and Safety Study of One Dose of GSK Biologicals' Meningococcal Vaccine GSK 134612 (Blinded Lots) Versus One Dose of Mencevax™ ACWY in Healthy Subjects Aged 18-25 Years

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

Intervention / Treatment
-----------------
* Biological: Mencevax ACWY
* Biological: GSK Biologicals' meningococcal serogroup A, C, W-135, Y tetanus toxoid conjugate investigational vaccine [GSK 134612]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All subjects must satisfy all of the following criteria at study entry: Subjects whom the investigator believes they can and will comply with the requirements of the protocol will be enrolled in the study. A male or female between, and including, 18 and 25 years of age the time of the vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. 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 vaccination. Exclusion Criteria: The following criteria should be checked at the time of study entry. If any exclusion criterion applies, the subject must not be included in the study: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination. (For corticosteroids, this will mean prednisone <10 mg/day, or equivalent, is allowed. Inhaled and topical steroids are allowed). Planned administration/administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine, with the exception of any licensed inactivated influenza vaccine, including H1N1 vaccine. Previous vaccination with meningococcal polysaccharide vaccine within the last five years. Previous vaccination with meningococcal conjugate vaccine. Previous vaccination with tetanus-toxoid or tetanus-toxoid containing vaccine within the last month. History of meningococcal disease. Seropositive for HIV or HBsAg (for subjects in the Philippines only). Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection, based on medical history and physical examination. A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient has been demonstrated. History of reactions or allergic disease likely to be exacerbated by any component of either vaccine. History of any neurologic disorders, including Guillain-Barré Syndrome. Major congenital defects or serious chronic illness. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the 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. Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 25 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: GSK Biologicals' meningococcal serogroup A, C, W-135, Y tetanus toxoid conjugate investigational vaccine [GSK 134612]<br>* One dose, Intramuscular injection<br>|
| Experimental: Group B<br> | Biological: GSK Biologicals' meningococcal serogroup A, C, W-135, Y tetanus toxoid conjugate investigational vaccine [GSK 134612]<br>* One dose, Intramuscular injection<br>|
| Active Comparator: Group C<br> | Biological: Mencevax ACWY<br>* One dose, Subcutaneous injection<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Vaccine Response for Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies | Vaccine response defined as: for initially seronegative subjects, antibody titer greater than or equal to (≥) 1:32 and for initially seropositive subjects: antibody titer ≥ 4 fold the pre-vaccination antibody titer. The analysis was performed with the GSK rSBA assay. | At Month 1 | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers | Titers are presented as geometric mean titers (GMTs). All subjects underwent testing with the GSK rSBA assay for all 4 serogroups. | At Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With 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. The analysis was performed with the Health Protection Agency (HPA) rSBA assay. | At Day 0 and at Month 1 | 
| Number of Subjects With 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 (≥) 1:128. The analysis was performed with the Health Protection Agency (HPA) rSBA assay. | At Day 0 and Month 1 | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers | Titers are presented as geometric mean titers (GMTs). The analysis was performed with the Health Protection Agency (HPA) rSBA assay. | At Day 0 and at Month 1 | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers Above the Cut-off Value | The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8. The analysis was performed with the GSK rSBA assay. | At Day 0 and at Month 1 | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers | Titers are presented as geometric mean titers (GMTs). The analysis was performed with the GSK rSBA assay. | At Day 0 | 
| Number of Subjects With Vaccine Response for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibodies | Vaccine response defined as: for initially seronegative subjects, antibody titer greater than or equal to (≥) 1:32 and for initially seropositive subjects: antibody titer ≥ 4 fold the pre-vaccination antibody titer. The analysis was performed with the Health Protection Agency (HPA) rSBA assay. | At Month 1 | 
| 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. | Within 4-days (Days 0-3) post-vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache and temperature [defined as orally temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. 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. | Within 4-days (Days 0-3) post-vaccination | 
| Number of Subjects With 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. | Within 31-days (Days 0-30) post-vaccination | 
| Number of Subjects With New Onset Chronic Illnesses (NOCI) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | Within 31-days (Days 0-30) post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adolescent, Vaccine, conjugate, Adult, Neisseria meningitidis, Immunogenicity, Meningococcal vaccine, Safety