Safety & Immunogenicity Study of Meningococcal Vaccine GSK134612 Given With Priorix-Tetra™ to 12-23 Month-Old Children

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate, in 12-23 month old children, the non-inferiority of the meningococcal vaccine 134612 given with Priorix-Tetra. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Open multicentre study with 4 treatment groups. Two groups will receive the 134612 vaccine with Priorix-Tetra either at the same or different visits followed by a second Priorix-Tetra vaccination at 84 days. Two control groups will receive Priorix-Tetra and Meningitec at different visits followed by a second Priorix-Tetra vaccination at 84 days. For all subjects, two blood samples will be taken: prior to and 42 days after the first vaccination. In a subset (30% of subjects in Groups A en C) from selected study centres: additional sample 42 days after second Priorix-Tetra dose.

Official Title
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Immunogenicity & Safety Study of GSK Biologicals' Meningococcal Vaccine GSK134612 When Co-Administered With GSK Biologicals' MMRV Vaccine (Priorix-Tetra™) in Healthy 12 to 23-Month-Old Children

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612 (Nimenrix)
* Biological: Priorix-Tetra
* Biological: Meningitec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. A male or female between, and including, 12 and 23 months of age at the time of the vaccination. Written informed consent obtained from the parent or guardian 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 parents' or legal guardians' knowledge. 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 vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within one month before and 42 days after the first dose of vaccine(s). Previous vaccination with meningococcal vaccine of serogroup A, C W and/or Y. History of meningococcal disease. Previous vaccination against measles, mumps, rubella, and/or varicella. History of measles, mumps, rubella and/or varicella. Known exposure to measles, mumps, rubella, varicella or zoster within 30 days prior to vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including human immunodeficiency virus (HIV) infection, based on medical history and physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including neomycin. 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 first dose of study vaccine or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 Months

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 + Priorix-Tetra Group<br>Subjects received 1 dose of Nimenrix vaccine and 1 dose of Priorix-Tetra vaccine on Day 0 and a second dose of Priorix-Tetra vaccine on Day 84. | Biological: Meningococcal vaccine GSK134612 (Nimenrix)<br>* Single dose intramuscular injection<br>Biological: Priorix-Tetra<br>* 2-dose subcutaneous injection<br>|
| Experimental: Nimenrix Group<br>Subjects received 1 dose of Nimenrix vaccine on Day 0 followed by 2 doses of Priorix-Tetra vaccine, respectively 42 and 84 days later. | Biological: Meningococcal vaccine GSK134612 (Nimenrix)<br>* Single dose intramuscular injection<br>Biological: Priorix-Tetra<br>* 2-dose subcutaneous injection<br>|
| Active Comparator: Priorix-Tetra Group<br>Subjects received 1 dose of Priorix-Tetra vaccine on Day 0, 1 dose of Meningitec vaccine on Day 42 and a second dose of Priorix-Tetra vaccine on Day 84. | Biological: Priorix-Tetra<br>* 2-dose subcutaneous injection<br>Biological: Meningitec<br>* Single dose intramuscular injection<br>|
| Active Comparator: Meningitec Group<br>Subjects received 1 dose of Meningitec vaccine on Day 0 followed by 2 doses of Priorix-Tetra vaccine, respectively 42 and 84 days later. | Biological: Priorix-Tetra<br>* 2-dose subcutaneous injection<br>Biological: Meningitec<br>* Single dose intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenC, rSBA-MenA, rSBA-MenW-135, rSBA-MenY Titers Greater Than or Equal to (≥) the Cut-off Values | The cut-off values for the rSBA titers were ≥ 1:8. The analysis was performed only on subjects receiving meningitis vaccination (Nimenrix) at Day 0. | 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With Anti-measles Antibody Concentrations ≥ the Cut-off Values | The cut-off values for anti-measles antibody concentrations were ≥ 150 milli-international units per milliliter (mIU/mL). | 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With Anti-mumps Antibody Concentrations ≥ the Cut-off Values | The cut-off values for anti-mumps antibody concentrations were ≥ 231 units per milliliter (U/mL). | 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With Anti-rubella Antibody Concentrations ≥ the Cut-off Values. | The cut-off values for anti-rubella antibody concentrations were ≥ 4 international units per milliliter (IU/mL). | 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With Anti-varicella Antibody Concentrations ≥ the Cut-off Values | The cut-off values for anti-varicella antibody concentrations were ≥ 1:4. | 42 days after the first vaccine dose (Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ the Cut-off Values | The cut-off values for the rSBA titers were ≥ 1:8 and ≥ 1:128 respectively. At pre-vaccination for all groups, half of the subjects were sera tested for rSBA-MenC while the other half was tested for rSBA-MenA, rSBA-MenW-135 and rSBA-MenY. At Post vaccination I (Day 42), all subjects from Nimenrix + Priorix-Tetra and Nimenrix groups were sera tested for each rSBA. For Meningitec and Priorix-Tetra groups, all subjects were tested for rSBA-MenC while half of subjects were tested for rSBA-MenA, rSBA-MenW-135 and rSBA-MenY. | Prior to vaccination (Day 0) and after the first vaccination dose (Day 42) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers | Antibody titers were expressed as geometric mean titers (GMTs). At pre-vaccination for all groups, half of the subjects were sera tested for rSBA-MenC while the other half were tested for rSBA-MenA, rSBA-MenW-135 and rSBA-MenY. At Post vaccination I (Day 42), all subjects from Nimenrix + Priorix-Tetra and Nimenrix groups were sera tested for each rSBA. For Meningitec and Priorix-Tetra groups, all subjects were tested for rSBA-MenC while half of subjects were tested for rSBA-MenA, rSBA-MenW-135 and rSBA-MenY. | Prior to first vaccine dose (Day 0) and 42 days after the first vaccine dose (Day 42) | 
| Anti-PSA (Anti-polysaccharide A), Anti-PSC, Anti-PSW-135 and Anti-PSY Antibodies Concentrations ≥ the Cut-off Values | Anti-PS antibody concentrations were given as geometric mean concentrations (GMCs) and expressed as microgram per milliliter (μg/mL). At pre-vaccination (Day 0) and Post-vaccination I (Day 42), a quarter of the subjects were tested for anti-PSC and another quarter for anti-PSA, anti-PSW-135 and anti-PSY. | Prior to the first vaccine dose (Day 0) and 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibodies Concentrations ≥ the Cut-off Values | The cut-off values for anti-PS antibody concentrations were ≥ 0.3 μg/mL and ≥ 2.0 μg/mL respectively. At pre-vaccination (Day 0) and Post-vaccination I (Day 42), a quarter of the subjects were tested for anti-PSC and another quarter for anti-PSA, anti-PSW-135 and anti-PSY. | Prior to first vaccine dose (Day 0) and 42 days after the first vaccine dose (Day 42) | 
| Number of Subjects With hSBA-MenA (Meningococcal Polysaccharide A Serum Bactericidal Antibodies Using Human Complement), hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers ≥ the Cut-off Values | The cut-off values for hSBA antibody titers were ≥ 1:4 and ≥ 1:8 for Nimenrix + Priorix-Tetra group, Nimenrix group, Meningitec group and Pooled group (Nimenrix + Priorix-Tetra and Nimenrix groups), respectively. The analysis was performed only on subjects receiving meningitis vaccination (Nimenrix) at Day 0. | Prior to first vaccine dose (Day 0) and 42 days after the first vaccine dose (Day 42) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers | Anti-hSBA antibody titers were expressed as geometric mean titers (GMTs) for Nimenrix + Priorix-Tetra group, Nimenrix group, Meningitec group and Pooled group (Nimenrix + Priorix-Tetra and Nimenrix groups), respectively. The analysis was performed only on subjects receiving meningitis vaccination (Nimenrix) at Day 0. | Prior to first vaccine dose (Day 0) and 42 days after the first vaccine dose (Day 42) | 
| Anti-measles Antibody Concentrations | Anti-measles antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL) in all groups. | 42 days after the first vaccine dose (Day 42) | 
| Anti-measles Antibody Concentrations | Anti-measles antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in mIU/mL in a subset (30%) of the Nimenrix + Priorix-Tetra and Priorix-Tetra groups only. The analysis was performed only on subjects receiving varicella vaccination (Priorix-Tetra) at Day 0. | 42 days after the second Priorix-Tetra vaccine dose (Day 126) | 
| Anti-mumps Antibody Concentrations | Anti-mumps antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in units per milliliter (U/mL) in all groups. | 42 days after the first vaccine dose (Day 42) | 
| Anti-mumps Antibody Concentrations | Anti-mumps antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in U/mL in a subset (30%) of the Nimenrix + Priorix-Tetra and Priorix-Tetra groups only. The analysis was performed only on subjects receiving varicella vaccination ( Priorix-Tetra) at Day 0. | 42 days after the second Priorix-Tetra vaccine dose (Day 126) | 
| Anti-rubella Antibody Concentrations | Anti-rubella antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in international units per millilier (IU/mL) in all groups. | 42 days after the first vaccine dose (Day 42) | 
| Anti-rubella Antibody Concentrations | Anti-rubella antibody concentrations were given as geometric mean concentrations (GMCs) and expressed in IU/mL in a subset (30%) of the Nimenrix + Priorix-Tetra and Priorix-Tetra groups only. The analysis was performed only on subjects receiving varicella vaccination (Priorix-Tetra) at Day 0. | 42 days after the second Priorix-Tetra vaccine dose (Day 126) | 
| Anti-varicella Antibody Titers | Anti-varicella antibody titers were given as geometric mean titers (GMTs) for all groups. | 42 days after the first vaccine dose (Day 42) | 
| Anti-varicella Antibody Titers | Anti-varicella antibody titers were given as geometric mean titers (GMTs) in a subset (30%) of the Nimenrix + Priorix-Tetra and Priorix-Tetra groups only. The analysis was performed only on subjects receiving varicella vaccination ( Priorix-Tetra) at Day 0. | 42 days after the second Priorix-Tetra vaccine dose (Day 126) | 
| Number of Subjects Reporting Solicited Local Symptoms Specific for Priorix-Tetra Vaccination | Solicited local symptoms assessed were pain, redness and swelling for the Nimenrix + Priorix-Tetra Group and Priorix-Tetra Group, respectively. The analysis was performed only on subjects receiving varicella vaccination (Priorix-Tetra) at Day 0. | During the 4-day (Days 0-3) after vaccination with first dose of Priorix-Tetra vaccine at Day 0 | 
| Number of Subjects Reporting Solicited Local Symptoms After Nimenrix or Meningitec Vaccination at Day 0 | Solicited local symptoms assessed were pain, redness and swelling for the Nimenrix + Priorix-Tetra Group, Nimenrix Group and Meningitec Group, respectively. The analysis was performed only on subjects receiving meningitis vaccination (Priorix-Tetra) at Day 0. | During the 4-day (Days 0-3) after vaccination with Nimenrix or Meningitec at Day 0 | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed were drowsiness, fever (measured rectally and temperature ≥ 38.0°C ), irritability and loss of appetite, Meningismus, Parotiditis and Rash. | During the 4-day (Days 0-3) follow-up period after first vaccination dose in all groups | 
| Number of Subjects With Priorix-Tetra - Specific Solicited General Symptoms | Solicited general symptoms assessed were fever (measured rectally and temperature ≥ 38.0°C ), Meningismus, Parotiditis and Rash. | During the 43-day (Days 0-42) after first vaccination dose | 
| Number of Subjects Reporting Specific Adverse Events (AEs) | Specific AEs include: rash, New Onset of Chronic Illness(es) (NOCI), and/or conditions prompting emergency room (ER) visits or non-routine physician office visits. | From Day 0 up to Month 6 after first vaccine dose | 
| Number of Subjects Reporting Unsolicited Symptoms | Unsolicited symptom covers any symptom 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. | During the 43-day (Days 0-42) post Dose 1 vaccination period | 
| Number of Subjects Reporting Unsolicited Symptoms | Unsolicited symptom covers any symptom 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. | During the 43-day (Days 0-42) follow-up period after each vaccination | 
| Number of Subjects Reporting 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. | From Day 0 up to Month 6 after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MMRV vaccine, co-administration, immunogenicity, meningococcal vaccine, conjugate vaccine