Primary Study to Demonstrate Non-inferiority and Immunogenicity of GSK Biologicals' Meningococcal Vaccine 134612

Study Overview
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Brief Summary
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This study will demonstrate the non-inferiority of GSK Biologicals' meningococcal vaccine 134612 when given in an experimental co-administration versus vaccine 134612 alone and versus the experimental co-administration alone in healthy subjects aged 11 through 17 years. There will be 3 groups in this study.

Detailed Description
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All subjects of groups A and B will have 4 blood samples taken, all subjects of group C will have 3 blood samples taken. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

Official Title
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Non-inferiority of GSK Biologicals' Meningococcal Vaccine 134612 Given Concomitantly With GSK Biologicals' Twinrix™ Versus 134612 Alone and Twinrix™ Alone in Healthy Subjects Aged 11 Through 17 Years.

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Nimenrix (Meningococcal vaccine 134612)
* Biological: Twinrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol A male or female between, and including, 11 and 17 years of age at the time of the first dose of vaccine. Written informed consent obtained from the subject/ from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Previously completed routine childhood vaccinations to the best of his/her/the parents'/guardians' knowledge. If the subject is female and of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first 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 first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine. Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W-135 and/or Y within the last five years. Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W-135 and/or Y. Previous vaccination with tetanus toxoid within the last month. Previous vaccination with hepatitis A and/or hepatitis B vaccine. Seropositivity for hepatitis A IgG, hepatitis B surface antigen, hepatitis B core antibody and/or hepatitis B surface antigen at screening. History of hepatitis A, hepatitis B and/or Neisseria meningitidis infection. Known exposure to hepatitis A and/or hepatitis B virus within three months preceding the first dose of study 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. A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated. History of reactions or allergic disease likely to be exacerbated by any component of either vaccine. 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.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 17 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: Nimenrix + Twinrix Group<br>Subjects received 1 dose of Nimenrix™ vaccine at Month 0 and 1 dose of Twinrix™ vaccine at Months 0, 1 and 6. | Biological: Nimenrix (Meningococcal vaccine 134612)<br>* Single dose intramuscular injection<br>Biological: Twinrix<br>* 3-dose intramuscular injection. Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.<br>|
| Active Comparator: Nimenrix Group<br>Subjects received 1 dose of Nimenrix™ vaccine at Month 0. | Biological: Nimenrix (Meningococcal vaccine 134612)<br>* Single dose intramuscular injection<br>|
| Active Comparator: Twinrix Group<br>Subjects received 1 dose of Twinrix™ vaccine at Months 0, 1 and 6. | Biological: Twinrix<br>* 3-dose intramuscular injection. Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Meningococcal Polysaccharide A Serum Bactericidal Antibodies/Assay, Using Baby Rabbit Complement for Assay (rSBA-MenA), rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers | The rSBA titers were expressed as geometric mean titers (GMTs). | At 1 month after vaccination with Nimenrix vaccine (Month 1) | 
| Number of Subjects Seroconverted for Hepatitis A | A seroconverted subject was defined as a subject with anti-Hepatitis A virus (HAV) antibody concentration greater than or equal to 15 milli-International Units per Milliliter (mIU/mL) in previously seronegative subjects. | At 1 month after the third dose of Twinrix vaccine (Month 7) | 
| Number of Subjects Seroprotected for Hepatitis B | A seroprotected subject was defined as a subject with anti-Hepatitis B surface antigen (HBs) antibody concentration greater than or equal to 10 milli-International Units per Milliliter (mIU/mL). | At 1 month after the third dose of Twinrix vaccine (Month 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Vaccine Response to MenA, MenC, MenY and MenW-135 | Vaccine response is defined as an rSBA titer of at least 1:32 in subjects initially seronegative [rSBA titer below1:8] and as a 4-fold increase in titer in subjects initially seropositive [rSBA titre greater than or equal to 1:8]. | At 1 month after vaccination with Nimenrix vaccine (Month 1) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Predefined Cut-off Values | The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128. | Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) | 
| Anti-PSA (Polysaccharide A), Anti-PSC (Polysaccharide C), Anti-PSW-135 (Polysaccharide W-135), and Anti-PSY (Polysaccharide Y) Antibody Concentrations | Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL). | Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135, and Anti-PSY Antibody Concentrations Above Pre-defined Cut-off Values | The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL. | Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) | 
| Anti-Tetanus Toxoid (TT) Antibody Concentrations | Concentrations were provided as Geometric Mean Concentrations expressed as International Units per milliliter (IU/mL). | Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) | 
| Number of Subjects With Anti-tetanus Toxoid Antibody Concentrations Above the Pre-defines Cut-off Value | The cut-off value assessed was greater than or equal to 0.1 International Units per milliliter (IU/mL). | Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers at Month 7 | The rSBA titers were expressed as geometric mean titers. | At 7 months after vaccination with Nimenrix (At Month 7) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Predefined Cut-off Values at Month 7 | The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128. | At 7 months after vaccination with Nimenrix (At Month 7) | 
| Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentrations at Month 7 | Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL). | At 7 months after vaccination with Nimenrix (At Month 7) | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentrations Above Pre-defined Cut-off Values at Month 7 | The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL. | At 7 months after vaccination with Nimenrix (At Month 7) | 
| Immunoglobulin G (IgG) Anti-HAV Antibody Concentrations | Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL). | Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) | 
| Number of Subjects With IgG Anti-HAV Antibody Concentrations Above the Pre-defined Cut-off Value | The cut-off value assessed was greater than or equal to 15 milli-Internatinal Units per Milliliter (mIU/mL). | Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) | 
| IgG Anti-HBs Antibody Concentrations | Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL). | Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) | 
| Number of Subjects With IgG Anti-HB Antibody Concentrations Above the Pre-defined Cut-off Value | The cut-off value assessed was greater than or equal to 10 milli-Internatinal Units per Milliliter (mIU/mL). | Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) | 
| Number of Subjects Reporting Any Solicited Local Symptoms Post-meningococcal Vaccination | Solicited local symptoms assessed include pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During a 4-day period (Days 0-3) after Nimenrix vaccination | 
| Number of Subjects Reporting Any Solicited Local Symptoms Post-Twinrix Vaccination | Solicited local symptoms assessed include pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During a 4-day period (Days 0-3) after each Twinrix vaccination, and across doses | 
| Number of Subjects Reporting Any Solicited General Symptoms | Solicited general symptoms assessed include fatigue, fever (axillary temperature greater than or equal to 37.5 degrees Celcius), gastrointestinal symptoms and headache. Any = occurrence of the symptom regardless of intensity grade. Dose 1 = post-Nimenrix and post-Twinrix for the Nimenrix + Twinrix Group, post-Twinrix for the Twinrix Group and post-Nimenrix for the Nimenrix Group, Dose 2, 3 and Across doses = post-Twinrix for the Nimenrix + Twinrix Group and for the Twinrix Group. | During a 4-day period (Days 0-3) after each vaccine dose and across doses | 
| Number of Subjects Reporting Any 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. | Up to 1 month after each vaccine dose | 
| Number of Subjects Reporting Any Specific AEs of New Onset of Chronic Illnesses | Specific AEs of new onset of chronic illnesses include e.g. autoimmune disorders, asthma, type I diabetes and allergies. | During the entire study (up to Month 7) | 
| Number of Subjects Reporting Any Rash | Rashes include e.g. hives, idiopathic thrombocytopenic purpura, petechiae. | During the entire study (up to Month 7) | 
| Number of Subjects Reporting Any Conditions Prompting Emergency Room Visits |  | During the entire study (up to Month 7) | 
| Number of Subjects Reporting Any Serious Adverse Events (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 entire study (up to Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-inferiority, adolescents, meningococcal vaccine