Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Conjugate Vaccine When Co-administered With Routine Vaccines in Healthy Infants and Toddlers

Study Overview
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Brief Summary
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This study evaluates the immunogenicity and safety of the meningococcal conjugate vaccine GSK 134612 in healthy infants, when co-administered with other infant vaccines, on three different dose schedules.

Detailed Description
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This protocol has been updated following Protocol Amendment 1 date 26 July 2011 leading to the update of enrollment, a secondary outcome measure, intervention and exclusion criteria sections.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Conjugate Vaccine (GSK 134612) When Co-administered With Routine Vaccines in Healthy Infants and Toddlers

Conditions
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Meningococcal Infection

Intervention / Treatment
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* Biological: Meningococcal vaccine GSK 134612
* Biological: SynflorixTM
* Biological: Infanrix-IPV/HiberixTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol. A male or female, 6 to 12 weeks (42-90 days) of age at the time of the first vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Born after a gestation period of at least 36 weeks. Exclusion Criteria: Child in care. Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Extended administration of immunosuppressants or other immune-modifying drugs since birth. Planned administration/administration of a vaccine not foreseen by the study protocol during the period 30 days before and after each study vaccine administration, with the exception of rotavirus vaccine and seasonal or pandemic influenza vaccine. 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 product. Previous vaccination against diphtheria , tetanus, pertussis, polio (with the exception of a birth dose of OPV), Haemophilus influenzae type b, Streptococcus pneumonia. History of receipt of meningococcal vaccine. Subjects who received a birth dose Hepatitis B vaccines within the 30 days before the administration of the first study vaccine. History of or intercurrent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b disease, pneumococcal and/or meningococcal disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, 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 th

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimenrix 3+1 Group<br>Subjects, male and female, received 4 doses of Nimenrix™ vaccine (3 doses at 2, 4 and 6 months of age followed by a booster dose at 15-18 months of age) and 4 doses of Synflorix™ and Infanrix-IPV/Hiberix™ vaccines (at 2, 4, 6 and 15-18 months of age). All vaccines were administered intramuscularly (IM) in the anterolateral region of the thigh. | Biological: Meningococcal vaccine GSK 134612<br>* Intramuscular injection<br>Biological: SynflorixTM<br>* Intramuscular injection<br>Biological: Infanrix-IPV/HiberixTM<br>* Intramuscular injection<br>|
| Experimental: Nimenrix 1+1 Group<br>Subjects, male and female, received 2 doses of Nimenrix™ vaccine (1 dose at 6 months of age followed by a booster dose at 15-18 months of age) and 4 doses of Synflorix™ and Infanrix-IPV/Hiberix™ vaccines (at 2, 4, 6 and 15-18 months of age). All vaccines were administered intramuscularly (IM) in the anterolateral region of the thigh. | Biological: Meningococcal vaccine GSK 134612<br>* Intramuscular injection<br>Biological: SynflorixTM<br>* Intramuscular injection<br>Biological: Infanrix-IPV/HiberixTM<br>* Intramuscular injection<br>|
| Experimental: Nimenrix Control Group<br>Subjects, male and female, received 1 dose of Nimenrix™ at 15-18 months of age and 4 doses of Synflorix™ and Infanrix-IPV/Hiberix™ vaccines (at 2, 4, 6 and 15-18 months of age). All vaccines were administered intramuscularly (IM) in the anterolateral region of the thigh. | Biological: Meningococcal vaccine GSK 134612<br>* Intramuscular injection<br>Biological: SynflorixTM<br>* Intramuscular injection<br>Biological: Infanrix-IPV/HiberixTM<br>* 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 Assay Using Rabbit Complement (rSBA) Against Neisseria Meningitidis Serogroups Antibody Titers Greater Than or Equal to (≥) 1:8, One Month Post Dose 3 for the Nimenrix 3+1 Group | The cut-off value for the rSBA titers was ≥ 1:8. Neisseria meningitidis serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) antibodies were assessed. | At Month 5 (one month post-dose 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers Greater Than or Equal to (≥) 1:8 Prior to and One Month After the Booster Dose for the Nimenrix 3+1 Group | The cut-off value for the rSBA titers was ≥ 1:8 | At Month 13 (prior booster) and at Month 14 (one month after the booster dose) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers Greater Than or Equal to (≥) 1:128, One Month Post-dose 3, Prior to and One Month After the Booster Dose for the Nimenrix 3+1 Group | The cut-off value for the rSBA titers was ≥ 1:128 | At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers One Month Post Dose 3, Prior to and One Month After the Booster Dose for the Nimenrix 3+1 Group | Antibody titers are presented as geometric mean titers (GMTs). | At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose) | 
| Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers Greater Than or Equal to (≥) the Cut-off Values for the Nimenrix 1+1 and Nimenrix Control Groups | The cut-off values for the rSBA antibody titers were ≥ 1:8 and ≥ 1:128 | At Months 5 (one month post-primary dose for Nimenrix 1+1 Group), 13 (prior booster dose for Nimenrix 1+1 and prior primary dose for Nimenrix Control Group) and 14 (post booster dose for Nimenrix 1+1 and post-primary dose for Nimenrix Control Group) | 
| rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers for Nimenrix 1+1 and Nimenrix Control Groups | Antibody titers are presented as geometric mean titers (GMTs). | At Months 5 (one month post-primary dose for Nimenrix 1+1 Group), 13 (prior booster dose for Nimenrix 1+1 and prior primary dose for Nimenrix Control Group) and 14 (post booster dose Nimenrix 1+1 and post-primary dose for Nimenrix Control Group) | 
| Number of Subjects With Booster Responses for rSBA-MenA, C rSBA-MenC, Y rSBA-MenY and W-135 rSBA-MenW-135 in Nimenrix 3+1 and Nimenrix 1+1 Groups and With Vaccine Response in Nimenrix Control Group | Vaccine/Booster response was defined as: for seronegative subjects (rSBA titers < 1:8 pre-vaccination at Month 13), antibody titer ≥ 1:32 at post vaccination; for seropositive subjects (rSBA titers >= 1:8 pre-vaccination at Month 13), antibody titer at post vaccination ≥ 4-fold the pre vaccination antibody titer. | At Month 14 (one month post-booster dose for Nimenrix 3+1 and Nimenrix 1+1 and post-primary dose for Nimenrix Control Group) | 
| Number of Subjects With Serum Bactericidal Assay Using Human Complement Against Neisseria Meningitidis Serogroups A, C, W-135, Y Antibody Titers Greater Than or Equal to (≥) the Cut-off Values (One Month Post-primary for Nimenrix 3+1 and 1+1 Groups) | The cut-off value for the hSBA titers was ≥ 1:4 and ≥ 1:8. | At Month 5 (one month post-primary for Nimenrix 3+1 and Nimenrix 1+1 Groups) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-Men-Y Antibody Titers (One Month Post-primary for Nimenrix 3+1 and Nimenrix 1+1 Groups)) -Randomized Subset of 50% of Subjects of All Three Groups | Antibody titers are presented as geometric mean titers (GMTs). | At Month 5 (one month post-primary for Nimenrix 3+1 and Nimenrix 1+1 Groups) | 
| Number of Participants With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-Men-Y Titers (≥) the Cut-off Value (Pre- and Post-booster for Nimenrix 3+1 and 1+1 Groups and Pre- and Post-vaccination for Nimenrix Control) | The cut-off value for the hSBA titers was ≥ 1:4 and ≥ 1:8. | At Month 13 (pre-booster for Nimenrix 3+1 and Nimenrix 1+1 Groups and pre-vaccination for Nimenrix Control), and at Month 14 (post-booster for Nimenrix 3+1 and Nimenrix 1+1 Groups and post-vaccination for Nimenrix Control) | 
| hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-Men-Y Antibody Titers (Pre-booster for Nimenrix 3+1 and 1+1 Groups and Pre-vaccination for Nimenrix Control, and Post-booster for Nimenrix 3+1 and 1+1 Groups and Post-vaccination for Nimenrix Control) | Antibody titers are presented as geometric mean titers (GMTs). | At Month 13 (pre-booster for Nimenrix 3+1 and Nimenrix 1+1 Groups and pre-vaccination for Nimenrix Control), and at Month 14 (post-booster for Nimenrix 3+1 and Nimenrix 1+1 Groups and post-vaccination for Nimenrix Control) | 
| Number of Subjects With Booster Responses for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY in Nimenrix 3+1 and Nimenrix 1+1 Groups and With Vaccine Response in Nimenrix Control Group | Vaccine/Booster response was defined as: for seronegative subjects (rSBA titers < 1:4 pre-vaccination at Month 13), antibody titer ≥ 1:32 at post vaccination; for seropositive subjects (rSBA titers >= 1:4 pre-vaccination at Month 13), antibody titer at post vaccination ≥ 4-fold the pre vaccination. | At Month 14 (one month after the booster dose in Nimenrix 3+1 and Nimenrix 1+1 and post-vaccination in Nimenrix Control Group) | 
| Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to (≥) 0.15 Micrograms Per Milliliter (µg/mL). | The anti-pneumococcal serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. | At Months 5 (one month post-dose 3), Month 13 (prior booster dose) and Month 14 (one month after the booster dose) | 
| Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to (≥) 0.35 Micrograms Per Milliliter (µg/mL) | The anti-pneumococcal serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. | At Months 5 (one month post-dose 3), Month 13 (prior booster dose) and Month 14 (one month after the booster dose) | 
| Anti-pneumococcal Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in micrograms/milliliter (µg/mL) | At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose) | 
| Number of Subjects With Anti-diphtheria (Anti-D) Antibodies | Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). | At Month 5 (one month post-dose 3) | 
| Concentration of Antibodies Against Diphtheria Antigens (Anti-D) | Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL). | At Month 5 (one month post-dose 3) | 
| Concentration of Antibodies Against Diphtheria Antigens (Anti-D) | Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL). The analysis was performed in a randomized subset of 25% of subjects of all three groups. Note: As the percentage of subjects with serological results excluded from the ATP cohorts was higher than 5%, a second analysis based on the total vaccinated cohorts (TVCs) (Primary and Booster) was performed to complement the ATP analysis. | At Month 5 (one month post-dose 3) | 
| Concentration of Antibodies Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA), Pertactin (Anti-PRN) Antigens | Concentrations are presented as geometric mean concentrations (GMCs) expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml). | At Month 5 (one month post-dose 3) | 
| Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN) Immunoglobulin G (IgG) Antibodies | Cut-off values assessed were greater than or equal to ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml). | At Month 5 (one month post-dose 3) | 
| Antibody Titers for Anti-polio Type 1, 2 and 3 Antibodies | Antibody titers are presented as geometric mean titers (GMTs). | At Month 5 (one month post-dose 3) | 
| Antibody Titers for Anti-polio Type 1, 2 and 3 Antibodies | Antibody titers are presented as geometric mean titers (GMTs). The analysis was performed in a randomized subset of 25% of subjects of all three groups. Note: As the percentage of subjects with serological results excluded from the ATP cohorts was higher than 5%, a second analysis based on the total vaccinated cohorts (TVCs) (Primary and Booster) was performed to complement the ATP analysis. | At Month 5 (one month post-dose 3) | 
| Number of Subjects With Anti-tetanus (Anti-T) Antibodies | Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). | At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose) | 
| Concentration of Antibodies Against Tetanus Antigens (Anti-T) | Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL). | At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose) | 
| Number of Subjects With Anti-tetanus (Anti-T) Antibodies | Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). The analysis was performed in a randomized subset of 25% of subjects of all three groups. Note: As the percentage of subjects with serological results excluded from the ATP cohorts was higher than 5%, a second analysis based on the total vaccinated cohorts (TVCs) (Primary and Booster) was performed to complement the ATP analysis. | At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose) | 
| Anti-PRP Antibody Concentrations (Geometric Mean Concentrations) in a Randomized Subset of 25% of the Subjects | The endpoints evaluating immunogenicity of the Hib component (anti-polyribosyl ribitol phosphate [anti-PRP] antibody concentrations) has been cancelled owing to the extended delay in the re-development and re-validation of the PRP assay. | At Month 5 (one month post-dose 3) | 
| Number of Subjects With Solicited Local Symptoms (Primary Phase) | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. | Within 8 days (Day 0-7) post primary vaccination | 
| Number of Subjects With Solicited Local Symptoms (Booster Phase) | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. | Within 8 days (Day 0-7) post booster vaccination | 
| Number of Subjects With Solicited General Symptoms (Primary Phase) | Assessed solicited general symptoms were temperature [defined as rectally temperature equal to or above 38 degrees Celsius (°C)], drowsiness, irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 8 days (Day 0-7) post primary vaccination | 
| Number of Subjects With Solicited General Symptoms (Booster Phase) | Assessed solicited general symptoms were temperature [defined as rectally temperature equal to or above 38 degrees Celsius (°C)], drowsiness, irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 8 days (Day 0-7) post booster vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) (Primary Phase) | 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. | Within 31 days (Day 0-30) post each primary vaccine dose | 
| Number of Subjects With Unsolicited Adverse Events (AEs) (Booster Phase) | 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. | Within 31 days (Day 0-30) post booster vaccination | 
| Number of Subjects With New Onset of Chronic Illnesses (NOCIs) | NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. | From Day 0 to Month 19 | 
| Number of Subjects With 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 Day 0 to Month 19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningococcal conjugate vaccine, serogroups A,C, W-135 or Y, meningococcal diseases, Immunogenicity, Neisseria meningitidis, co-administration, routine vaccines