Co-Administration of Meningococcal Vaccine GSK134612 With Infanrix Hexa™ Versus Individual Administration of Each Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate, in 12-23 months old subjects, the non-inferiority of meningococcal vaccine GSK134612 co-administered with Infanrix hexa™, compared to each vaccine administered individually and to licensed meningococcal vaccine Meningitec™. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Multicentre study with 4 parallel groups. One group will receive GSK134612 co-administered with Infanrix hexa™, two groups will receive sequential administration of GSK134612 and Infanrix hexa™ and the final group will receive Meningitec™. For subjects in Groups B and C, three blood samples will be taken: prior to first vaccination and 1 month after each vaccination. For subjects in Groups A and D, two blood samples will be taken: prior to and 1 month after vaccination.

Official Title
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Co-Administration of GSK Biologicals' Meningococcal Vaccine GSK134612 With Infanrix Hexa™, Compared to Individual Administration of Each Vaccine, in Healthy 12- Through 23-Month-Old Children

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK134612
* Biological: Infanrix™ hexa
* 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 first 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. Documented three-dose primary vaccination with DTPa, hepatitis B, inactivated polio and Haemophilus influenzae type b conjugate vaccines, completed at least 180 days before administration of the first study vaccination. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines 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 any vaccine not foreseen by the study protocol, including measles, mumps, rubella, varicella and pneumococcal vaccines, within 30 days before the first dose of vaccine(s) and 30 days after the last dose of vaccine(s). Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W and/or Y. Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W and/or Y. Previous booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis or Haemophilus influenzae type b. 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. History of reactions or allergic disease likely to be exacerbated by any component of the vaccine(s). 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. Additional criteria for subjects receiving Infanrix hexa™ Hypersensitivity reaction due to previous vaccination with Infanrix hexa™. Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalised or focal seizures that persist more than a few hours, with failure to recover within 24 hours.

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: Group A<br>Meningococcal vaccine GSK134612 co-administered with Infanrix hexa™ | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection<br>Biological: Infanrix™ hexa<br>* Single dose intramuscular injection<br>|
| Experimental: Group B<br>Meningococcal vaccine GSK134612 followed one month later by Infanrix hexa™ | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection<br>Biological: Infanrix™ hexa<br>* Single dose intramuscular injection<br>|
| Active Comparator: Group C<br>Infanrix hexa™ followed one month later by Meningococcal vaccine GSK134612 | Biological: Meningococcal vaccine GSK134612<br>* Single dose intramuscular injection<br>Biological: Infanrix™ hexa<br>* Single dose intramuscular injection<br>|
| Active Comparator: Group D<br>Meningitec™ vaccination | 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-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ the Cut-off. | The cut-off for the assay was greater than or equal to (≥) 1:8. The analysis was based only on subjects receiving Nimenrix vaccination at Day 0. | 1 month after vaccination with Nimenrix vaccine (Month 1) | 
| Anti-PT, Anti-FHA and Anti-PRN Concentrations | The analysis was based only on subjects receiving Infanrix-hexa vaccination. The results were calculated as geometric mean expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | 1 month after the first vaccination (Month 1) | 
| Number of Subjects With Anti-HBs Concentrations ≥ the Cut-off | The cut-off for the assay was greater than or equal to (≥) 10 milli-interantional units per milliliter (mIU/mL). | 1 month after vaccination with Nimenrix vaccine (Month 1) | 
| Number of Subjects With Anti-PRP Concentrations ≥ the Cut-off | The cut-off for the assay was ≥ 1μg/mL. | 1 month after vaccination with Nimenrix vaccine (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 Titers ≥ the Cut-off Values | The cut-off values for the assay were ≥ 1:8 and ≥ 1:128 | At month 0, month 1 and month 2 | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers | The results were tabulated as geometric mean expressed in titers. | At month 0, month 1 and month 2 | 
| Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off | The cut-off for the assay were ≥ 0.3 microgram per milliliter (μg/mL) and ≥ 2.0 μg/mL, respectively. | At month 0, month 1 and month 2 | 
| Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations | The results for the assay were tabulated as geometric mean expressed in microgram per milliliter (μg/mL). | At month 0, month 1 and month 2 | 
| Number of Seroprotected Subjects for Anti-tetanus Toxoid (Anti-TT) | The cut-off for the assay was ≥ 0.1 | At month 0, month 1 and month 2 | 
| Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations | The results for the assay were tabulated as geometric mean expressed in internationl units per milliliter (IU/mL). | At month 0, month 1 and month 2 | 
| Number of Subjects Seroprotected for Anti-diphtheria (Anti-D) ≥ the Cut-off | The cut-off for the assay was ≥ 0.1 | At month 0, month 1 and month 2 | 
| Anti-diphtheria (Anti-D) Antibody Concentrations | The results for the assay were tabulated as geometric mean expressed in internationl units per milliliter (IU/mL). | At month 0, month 1 and month 2 | 
| Number of Subjects Seroprotected for Anti-polio Type 1, 2 & 3 ≥ the Cut-off | The cut-off for the assay was ≥ 1:8. | At month 0, month 1 and month 2 | 
| Anti-polio Type 1, 2 & 3 Titers | The results for the assay were tabulated as geometric mean expressed in titers. | At month 0, 1 and 2 | 
| Numbers of Seroprotected Subjects for Anti-PRP ≥ the Cut-off | The cut-off for the assay was ≥ 1.0 | At month 0, month 1 and month 2 | 
| Anti-PRP Antibody Concentrations | The results for the assay were tabulated as geometric mean expressed in microgram per milliliter (μg/mL). | At month 0, month 1 and month 2 | 
| Number of Seroprotected Subjects for Anti-HBs ≥ the Cut-offs | The cut-offs for the assay were ≥ 10 mIU/mL and ≥ 100 mIU/mL respectively . | At month 0, month 1 and month 2 | 
| Anti-HBs Antibody Concentrations | The results for the assay were tabulated as geometric mean expressed in milli-international units per milliliter (mIU/mL). | At month 0, month 1 and month 2 | 
| Number of Subjects With a Vaccine Response to PT, FHA and PRN Antigens | Vaccine response to these antigens is defined as appearance of antibodies in subjects who were seronegative (antibody concentration < 5 EL.U/mL) at pre-vaccination or as at least a 2-fold increase in post-over pre-vaccination antibody concentrations in subjects seropositive at pre-vaccination. The analysis was based only on subjects receiving experimental vaccination. | 1 month after vaccination (Month 1) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | The results were tabulated as geometric mean expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At month 0, month 1 and month 2 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of any local symptom irrespective of intensity grade. Grade 3 Pain was defined as crying when limb was moved/ spontaneously painful. | During the 4-day (Days 0-3) follow-up period after Nimenrix or Meningitec vaccination | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Post-combined Diphtheria Vaccination | The analysis was based only on subjects receiving combined-diphtheria vaccination. | During the 4-day (Days 0-3) follow-up period after Infanrix-hexa vaccination | 
| Number of Subjects Reporting Any Solicited General Symptoms Following Each Dose | Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Any was defined as occurrence of any general symptom irrespective of intensity grade and relationship. Subjects in the Nimenrix + Infanrix-hexa Group did not receive a second dose of vaccination. | During the 4-day (Days 0-3) post-vaccination dose 1 (D1) and second dose (D2) | 
| Number of Subjects Reporting Any Rash | Any was defined as occurrence of at least one symptom experienced. | Day 0 - Month 7 | 
| Number of Subjects Reporting Any New Onset of Chronic Illnesses (NOCIs) | Any was defined as occurrence of at least one symptom experienced. | Day 0 - Month 7 | 
| Number of Subjects Reporting Any Conditions Prompting Emergency Room Visits (ER) | Any was defined as occurrence of at least one symptom experienced. | Day 0 - Month 7 | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) After the First Dose | An AE is 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. Any was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | Occurring within Day 0-30 following vaccination | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) After the Second Dose | An AE is 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. Any was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. The analysis was based only on subjects receiving a second dose of vaccination. | Occurring within Day 0-30 following vaccination | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. | From dose 1 (Month 0) up to study end (Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal vaccine, Immunogenicity, Routine infancy vaccination, Safety