Immunogenicity, Reactogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' MenACWY-TT Vaccine Administered 6 Years Post-MenC Primary Vaccination in Healthy Subjects Who Were 12-18 Months at Primary Vaccination

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity, reactogenicity and safety of a booster dose of GSK Biologicals' MenACWY-TT vaccine administered at 6 years post-primary vaccination with either GSK Biologicals' Hib-MenC-TT vaccine (Menitorix™) or Hiberix™ and Meningitec™, in healthy subjects aged 12-18 months at primary vaccination and to evaluate the long-term antibody persistence at 2 years after MenACWY-TT booster vaccination. This is an extension study of the Hib-MenC-TT-016 study (NCT number: NCT00326118).

Official Title
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The Vaccine Response and Long-term Antibody Persistence of GSK Biologicals' MenACWY-TT Vaccine (GSK134612) Administered as One Dose at 6 Years Post-MenC Primary Vaccination in Healthy Subjects Aged 12-18 Months at Primary Vaccination

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal conjugate vaccine GSK134612


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. A male or female between, and including, 84 and 95 months of age at the time of the booster vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject and written informed assent obtained from the subject in accordance with local laws and regulations. Healthy subjects as established by medical history and history-directed physical examination before entering into the study. Having completed the vaccination in the study [Hib-MenC-TT-016 (106445)] as per protocol. Exclusion Criteria: Child in care. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 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 the vaccine dose. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after the study vaccine dose, with the exception of a licensed inactivated influenza vaccine which can be administered at any time during the study according to the local recommendations. 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. Previous vaccination with meningococcal vaccine except the meningococcal vaccination received in the Hib-MenC-TT-016 study. History of meningococcal disease. 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. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine, and history of serious allergic reaction (anaphylaxis) following the administration of vaccine(s). Major congenital defects or serious chronic illness. History of any neurological disorders or seizures, including GBS. History of a simple, single febrile seizure is permitted. Acute disease and/or fever at the time of enrollment. Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, 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. Administration of immunoglobulins and/or any blood products within the 3 months preceding the study vaccination or planned administration during the booster vaccination phase of the study (i.e. between Visit 1 and Visit 2) and within 3 months preceding the blood sampling at Visit 3. The following criteria should be checked for the long-term persistence phase at two years after booster vaccination (Visit 3): In case an exclusion criterion becomes applicable, the subject will not enter the long-term follow-up and the reason will be documented. Previous administration of a meningococcal vaccine with the exception of the meningococcal vaccination given in the primary study and the booster vaccination in this particular study. History of meningococcal disease.

Ages Eligible for Study
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Minimum Age: 84 Months
Maximum Age: 95 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menitorix Group<br>Subjects who were primed with Menitorix™ (Hib-MenC-TT) + Priorix™ (MMR) vaccines in the primary study HIB-MENC-TT-016 (NCT00326118) received one dose of Nimenrix™ (MenACWY-TT) booster vaccine at Month 72 post primary vaccination (booster visit 1). The MenACWY-TT vaccine was administered intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Meningococcal conjugate vaccine GSK134612<br>* Single dose to be administrated intramuscularly in the deltoid of the non-dominant arm<br>|
| Experimental: Meningitec + Hiberix Group<br>Subjects who were primed with Meningitec™ (MCC) + Hiberix™ (Hib) + Priorix™ (MMR) vaccine in the primary study HIB-MENC-TT-016 (NCT00326118) received one dose of Nimenrix™ (MenACWY-TT) booster vaccine at Month 72 post primary vaccination (booster visit 1). The MenACWY-TT vaccine was administered intramuscularly (IM) in the deltoid region of the non-dominant arm. | Biological: Meningococcal conjugate vaccine GSK134612<br>* Single dose to be administrated intramuscularly 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 |
| --- | --- | --- |
| Number of Subjects With Vaccine Response for Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroup A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY) | Vaccine response was defined as: For initially seronegative subjects (pre-vaccination rSBA titer below 1:8), antibody titer greater than or equal to (≥) 1:32 at post-vaccination; for initially seropositive subjects, antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer. | At Month 73, one month post-booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | During the 31-day (Days 0-30) post-booster vaccination period at Month 72 | 
| 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. | During the 31-day (Days 0-30) post-booster vaccination period at Month 72 | 
| 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 Month 72 up to study end, at Month 96 | 
| Antibody Concentrations Against Tetanus (Anti-T) Antigen | Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). | At Month 73, one month post-booster vaccination | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers ≥ the Predefined Cut-off Values | The cut-off values for the rSBA titers were greater than or equal to (≥) 1:8 and 1:128. | At Month 96, 24 months post-booster vaccination | 
| Antibody Titers Against rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBa-MenY | Antibody titers were presented as geometric mean titers (GMTs). | At Month 96, 24 months post-booster vaccination | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms included pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) post-booster vaccination period at Month 72 | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, and fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) post-booster vaccination period at Month 72 | 
| Number of Subjects Reporting New Onset of Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | During the 31-day (Days 0-30) post-booster vaccination period at Month 72 | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers ≥ the Predefined Cut-off Values | The cut-off values for the rSBA titers were greater than or equal to (≥) 1:8 and 1:128. | At Month 73, one month post-booster vaccination | 
| Antibody Titers Against rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY | Antibody titers were presented as geometric mean titers (GMTs). | At Month 73, one month post-booster vaccination | 
| Number of Subjects With Anti-tetanus (Anti-T) Concentrations ≥ the Predefined Cut-off Values | The cut-off values for anti-T concentrations were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL) and ≥ 1 IU/mL. | At Month 73, one month post-booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Booster, Healthy, Vaccine response, Safety, Neisseria meningiditis, Antibody persistence, Meningococcal conjugate vaccine