Immuno,Safety of GSK Vaccine 134612 Given at Age of 12-15 Months 15-18 Months Post-priming With GSK Vaccine 792014

Study Overview
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Brief Summary
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The purpose of the study is to characterize the immunogenicity & safety of a booster dose of GSK Biologicals' meningococcal vaccine 134612 given at 12-15 months of age or at 15-18 months of age (co-administered with Infanrix®) in healthy toddlers primed with GSK Biological's Hib-meningococcal vaccine 792014. This study is single-blinded for the primary phase and open-label for the booster phase.

Detailed Description
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The purpose of this study is to evaluate the titer of antibody for serogroups A, C, Y and W-135 and the safety of a booster dose of GSK Biologicals' meningococcal vaccine 134612 given to toddlers who were primed with GSK Biological's Hib-meningococcal vaccine 792014. In addition, this study will provide immunogenicity and safety data on the co-administration of Infanrix with meningococcal vaccine 134612 as compared to Infanrix administered alone. Depending on the group the subject is assigned to, one or two blood samples will be taken out of the subject's arm during the study. The protocol posting has been updated following a protocol amendment.

Official Title
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Immunogenicity and Safety Study of a Booster Dose of GSK Biologicals' Meningococcal Vaccine 134612 Given at 12-15 Months of Age or at 15-18 Months of Age (Co-administered With Infanrix®) in Primed Healthy Toddlers.

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: GSK Biologicals' Meningococcal vaccine GSK134612 (Nimenrix)
* Biological: GSK Biologicals' Hib-meningococcal vaccine GSK 792014 (Menhibrix)
* Biological: Infanrix®
* Biological: ActHIB®
* Biological: Pediarix®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol. A male or female between, and including, 6 and 12 weeks of age (+ 6 days) at the time of the first vaccination. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Born after 36 weeks gestation. For inclusion in the booster phase, subjects must have received all three doses in the primary phase. Exclusion Criteria: Exclusion criteria for enrolment (primary phase) 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 since birth. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s). Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, and/or poliovirus; more than one previous dose of hepatitis B vaccine. History of Neisseria meningitidis, hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, polio or pertussis diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, or by dry natural latex rubber. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at time of enrollment. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Concurrent participation 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 (pharmaceutical product or device). Exclusion criteria for enrolment (booster phase) Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding entry into the booster phase (Visit 4), or planned use during the study period. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of entry into the booster phase (Visit 4) with the exception of Prevnar® and Hib (see the following three criteria) (Note; licensed influenza vaccine is allowed throughout the study) Planned administration/administration of a fourth dose of Prevnar® within 30 days of a booster dose of Infanrix® Previous administration of a booster dose of Hib prior to entry to the booster phase. Previous administration of a primary dose of Hib vaccine that is not part of the study protocol. Previous vaccination against Neisseria meningitidis that is not part of the study protocol. Previous vaccination with diphtheria, tetanus and pertussis antigens outside of the primary phase of the study. History of Neisseria meningitidis, Hib, diphtheria, tetanus or pertussis diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, or by dry natural latex rubber. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at time of enrollment. Administration of immunoglobulins and/or any blood products within the past 3 months or planned administration during the study period. Concurrent participation 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 (pharmaceutical product or device).

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menhibrix 1 Group<br>Subjects received 3 doses of Menhibrix vaccine and 3 doses of Pediarix vaccine at 2, 4 and 6 months of age during the Primary Vaccination Phase. For the Booster Vaccination Phase, subjects were re-randomized and received either 1 dose of Nimenrix vaccine (at 12-15 months of age) and 1 dose of Infanrix vaccine (at 15-18 months of age) [Nimenrix 1 Group] or a fourth dose of Menhibrix vaccine (at 12-15 months of age) and 1 dose of Infanrix vaccine (at 15-18 months of age) [Menhibrix 2 Group], or 1 dose of Nimenrix vaccine co-administered with 1 dose of Infanrix vaccine (at 15-18 months of age) [Nimenrix 2 Group]. | Biological: GSK Biologicals' Meningococcal vaccine GSK134612 (Nimenrix)<br>* One dose in the booster phase as intramuscular injection<br>* Other names: Nimenrix;Biological: GSK Biologicals' Hib-meningococcal vaccine GSK 792014 (Menhibrix)<br>* Three doses in the priming phase and, for Menhibrix 2 Group, one dose in the booster phase as intramuscular injection<br>* Other names: Menhibrix;Biological: Infanrix®<br>* One dose as intramuscular injection<br>Biological: Pediarix®<br>* Three doses in the priming phase as intramuscular injection<br>|
| Active Comparator: ActHIB- Infanrix Group<br>Subjects received 3 doses of ActHIB vaccine and 3 doses of Pediarix vaccine at 2, 4 and 6 months of age and 1 booster dose of Infanrix vaccine at 15-18 months of age. | Biological: Infanrix®<br>* One dose as intramuscular injection<br>Biological: ActHIB®<br>* Three doses in the priming phase as intramuscular injection<br>Biological: Pediarix®<br>* Three doses in the priming phase as 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 Serum Bactericidal Activity Using Human Complement (hSBA) Antibody Titers for N. Meningitidis Serogroups A(MenA), W-135(MenW-135), C(MenC) and Y(MenY) Greater Than or Equal to Protocol Specified Cut-off Value in Nimenrix 1 Group | The cut-off values assessed for hSBA-MenA, hSBA-MenW-135, hSBA-MenC and hSBA-MenY were greater than or equal to (≥) 1:8 | One month post vaccination at 12-15 months of age (Month 11) | 
| Number of Subjects With hSBA-MenA, hSBA-MenW-135, hSBA-MenC and hSBA-MenY Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Value in Nimenrix 2 Group | The cut-off values assessed for hSBA-MenA, hSBA-MenW-135, hSBA-MenC and hSBA-MenY were greater than or equal to (≥) 1:8 | One month post vaccination at 15-18 months of age (Month 14) | 
| Geometric Mean Antibody Titers for hSBA-MenC and hSBA-MenY in Nimenrix 1 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | One month post vaccination at 12-15 months of age (Month 11) | 
| Geometric Mean Antibody Titers for hSBA-MenC and hSBA-MenY in Nimenrix 2 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | One month post vaccination at 15-18 months of age (Month 14) | 
| Number of Subjects With Anti-Diptheria (Anti-D) and Anti-Tetanus (Anti-T) Antibody Concentrations Greater Than or Equal to Protocol Specified Cut-off Value in Nimenrix 2 Group and ActHIB- Infanrix Group | The cut-off value assessed for Anti-D and Anti-T were greater than or equal to (≥) 1.0 International Units per milliliter (IU/mL). | One month post vaccination at 15-18 months of age (Month 14) | 
| Geometric Mean Antibody Titers for hSBA-MenC and hSBA-MenY in Menhibrix 2 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | One month post vaccination at 12-15 months of age (Month 11) | 
| Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Value in Menhibrix 2 Group | The cut-off values assessed for hSBA-MenC and hSBA-MenY were greater than or equal to (≥) 1:8 | One month post vaccination at 12-15 months of age (Month 11) | 
| Geometric Mean Antibody Concentrations for Anti-PT (Pertusis Toxoid), Anti-FHA (Filamentous Hemagglutinin) and Anti-PRN (Pertactin) in Nimenrix 2 Group and ActHIB- Infanrix Group | Concentrations were provided as Geometric mean concentrations (GMCs) and expressed as enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) | One month after vaccination at 15-18 months of age (Month 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Values in Nimenrix 1 Group and Menhibrix 2 Group | The cut-off values assessed for hSBA-MenC and hSBA-MenY were greater than or equal to (≥) 1:4 | One month after vaccination at 12-15 months of age (Month 11) | 
| Number of Subjects With hSBA-MenA and hSBA MenW-135 Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Values in Nimenrix 1 Group | The cut-off values assessed for hSBA-MenA and hSBA-MenW-135 were greater than or equal to (≥) 1:4 | One month after vaccination at 12-15 months of age (Month 11) | 
| Geometric Mean Antibody Titers for hSBA-MenA and hSBA MenW-135 in Nimenrix 1 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | One month after vaccination at 12-15 months of age (Month 11) | 
| Geometric Mean Antibody Titers for hSBA-MenC and hSBA-MenY in Nimenrix 2 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | Prior to vaccination at 15-18 months of age (Month 13) | 
| Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Values in Nimenrix 2 Group | The cut-off values assessed for hSBA-MenC and hSBA-MenY were greater than or equal to (≥) 1:4 and ≥ 1:8 | Prior to vaccination at 15-18 months of age (Month 13) | 
| Anti-D and Anti-T Geometric Mean Antibody Concentrations | Concentrations were provided as Geometric Mean Concentrations(GMCs) and expressed as International Units per milliliter (IU/mL). | One month after vaccination with Infanrix at 15-18 months of age (Month 14) | 
| Number of Subjects With Anti-D and Anti-T Antibody Concentrations Greater Than or Equal to Protocol Specified Cut-off Value | The cut-off value assessed for Anti-D and Anti-T were greater than or equal to (≥) 0.1 International Units per milliliter (IU/mL). | One month after vaccination with Infanrix at 15-18 months of age (Month 14) | 
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations Greater Than or Equal to Protocol Specified Cut-off Value | The cut-off values assessed were greater than or equal to (≥) 5 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) | One month after vaccination with Infanrix at 15-18 months of age (Month 14) | 
| Geometric Mean Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN in Nimenrix 1 Group and Menhibrix 2 Group | Concentrations were provided as Geometric mean concentrations (GMCs) and expressed as enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) | One month after vaccination at 15-18 months of age (Month 14) | 
| Number of Subjects With Anti-D and Anti-T Antibody Concentrations Greater Than or Equal to Protocol Specified Cut-off Value in Nimenrix 1 Group and Menhibrix 2 Group | The cut-off values assessed for Anti-D and Anti-T were greater than or equal to (≥) 1.0 International Units per milliliter (IU/mL). | One month after vaccination at 15-18 months of age (Month 14) | 
| Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Greater Than or Equal to Protocol Specified Cut-off Values in Nimenrix 2 Group | The cut-off values assessed for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY were greater than or equal to (≥) 1:4 | One month after vaccination at 15-18 months of age (Month 14) | 
| Geometric Mean Antibody Titers for hSBA-MenA and hSBA-MenW-135 in Nimenrix 2 Group | Antibody titers were expressed as Geometric mean titers (GMTs) | One month after vaccination with Infanrix at 15-18 months of age (Month 14) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Following Each Dose With Nimenrix or Menhibrix Vaccine | Any was defined as any solicited local symptom reported regardless of intensity grade. Grade 3 redness and swelling was greater than (>) 30 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. | During the 8-day follow-up period (Day 0-7) after vaccination in the booster phase | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs in the Booster Phase | Any fever was defined as axillary temperature greater than or equal to 38.0 degree centigrade i.e ≥38.0°C, grade 3 fever was axillary temperature > 40.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination. | During the 8-day follow-up period (Day 0-7) after dose 4 and dose 5 vaccination | 
| Number of Subjects Reporting Any Rash | Examples of rash included hives, idiopathic thrombocytopenic purpura, petechiae. | From the first booster phase visit up to six months after the last vaccination (Month 10-13 up to Month 19-22) | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) Following Vaccination With Infanrix Vaccine | Any was defined as any solicited local symptom reported regardless of intensity grade. Grade 3 redness and swelling was > 30 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. | During the 8-day follow-up period (Day 0-7) after vaccination in the booster phase | 
| Number of Subjects Reporting Any New Onset of Chronic Illness (NOCI) and Any Emergency Room (ER) Visits | NOCIs include autoimmune disorders, asthma, type I diabetes and allergies. AEs prompting emergency room visits or physician visits are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. | From the first booster phase visit up to six months after the last vaccination (Month 10-13 up to Month 19-22) | 
| Number of Subjects Reporting Any New Onset of Chronic Illness (NOCI) and Any Emergency Room (ER) Visits | NOCIs include autoimmune disorders, asthma, type I diabetes and allergies. AEs prompting emergency room visits or physician visits are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. | From the first primary study dose up to/excluding the first booster study dose (Month 0 up to Month 10-13) | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) After the First or Single Booster Phase Vaccination | 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. | During a 31-day follow-up period (Day 0-30) | 
| Number of Subjects Reporting Any Unsolicited AEs in Nimenrix 1 Group and Menhibrix 2 Group After the Second Booster Phase Vaccination | 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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. | During the 31-day follow-up period (Day 0-30) | 
| Number of Subjects Reporting Any and Related 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | From the first primary study dose up to/excluding the first booster study dose (Month 0 up to Month 10-13). | 
| Number of Subjects Reporting Any and Related 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | From the first booster phase visit up to six months after the last vaccination (Month 10-13 up to Month 19-22) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal disease, Toddlers, Neisseria meningitidis, Meningococcal vaccines, Immunogenicity, Human serum bactericidal assay, Safety, Vaccines, conjugate, Booster vaccination