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

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.

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available. This endpoint was specified to be analysed for the Nimenrix 3+1 Group only.

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.

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on the Primary TVC, which included all vaccinated subjects during the primary phase.

Antibody titers are presented as geometric mean titers (GMTs).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on a randomized subset of 25% in the primary ATP cohort for immunogenicity who complied with the protocol criteria and for whom data concerning immunogenicity endpoint measures were available, for antibodies against at least one study vaccine antigen component after at least one vaccination during the primary vaccination.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) and measured in micrograms/milliliter (µg/mL)

Time frame: At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 25% of all 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.

Time frame: At Month 5 (one month post-dose 3)

Population: No subjects were analyzed because 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.

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.

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on the Primary TVC, which included all vaccinated subjects during the primary phase.

Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on a randomized subset of 25% in the primary ATP cohort for immunogenicity who complied with the protocol criteria and for whom data concerning immunogenicity endpoint measures were available, for antibodies against at least one study vaccine antigen component after at least one vaccination during the primary vaccination.

Concentrations are presented as geometric mean concentrations (GMCs) expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on the Primary TVC, which included all vaccinated subjects during the primary phase.

Concentrations are presented as geometric mean concentrations (GMCs) expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on a randomized subset of 25% in the primary ATP cohort for immunogenicity who complied with the protocol criteria and for whom data concerning immunogenicity endpoint measures were available, for antibodies against at least one study vaccine antigen component after at least one vaccination during the primary vaccination.

Concentrations are presented as geometric mean concentrations (GMCs) expressed in international units per milliliter (IU/mL).

Time frame: At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose)

Population: The analysis was performed on the ATP cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 25% of subjects of all three groups.

Antibody titers are presented as geometric mean titers (GMTs).

Time frame: At Month 5 (one month post-primary for Nimenrix 3+1 and Nimenrix 1+1 Groups)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 50% of subjects from each group.

Antibody titers are presented as geometric mean titers (GMTs).

Time frame: 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)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 75% of subjects from each group.

The cut-off value for the hSBA titers was ≥ 1:4 and ≥ 1:8.

Time frame: 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)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 75% of subjects from each group.

Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on a randomized subset of 25% in the primary ATP cohort for immunogenicity who complied with the protocol criteria and for whom data concerning immunogenicity endpoint measures were available, for antibodies against at least one study vaccine antigen component after at least one vaccination during the primary vaccination.

Cut-off values assessed were greater than or equal to ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/ml).

Time frame: At Month 5 (one month post-dose 3)

Population: The analysis was performed on the Primary TVC included all vaccinated subjects during the primary phase.

The anti-pneumococcal serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

Time frame: At Months 5 (one month post-dose 3), Month 13 (prior booster dose) and Month 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 25% of all subjects.

The anti-pneumococcal serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

Time frame: At Months 5 (one month post-dose 3), Month 13 (prior booster dose) and Month 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 25% of all subjects.

Cut-off values assessed were greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).

Time frame: At Months 5 (one month post-dose 3), Month 13 (prior booster-dose) and Month 14 (one month after the booster dose)

Population: The analysis was performed on the ATP cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 25% of subjects of all three groups.

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.

Time frame: At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose)

Population: The analysis was performed on the Adapted TVC, which included all vaccinated subjects during the primary phase.

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.

Time frame: At Month 14 (one month after the booster dose in Nimenrix 3+1 and Nimenrix 1+1 and post-vaccination in Nimenrix Control Group)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 75% of subjects from each 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.

Time frame: At Month 14 (one month post-booster dose for Nimenrix 3+1 and Nimenrix 1+1 and post-primary dose for Nimenrix Control Group)

Population: The analysis was performed on the Booster According-to-Protocol (ATP) cohort for immunogenicity, which included all eligible subjects, who complied with the vaccination schedule at Month 13 (booster dose for Nimenrix 3+1 and Nimenrix 1+1 and first dose in Nimenrix Control) and for whom data concerning immunogenicity endpoint measures were available

NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.

Time frame: From Day 0 to Month 19

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects during the primary phase.

The cut-off value for the rSBA titers was ≥ 1:128

Time frame: At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available.

The cut-off value for the rSBA titers was ≥ 1:8

Time frame: At Month 13 (prior booster) and at Month 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available.

The cut-off values for the rSBA antibody titers were ≥ 1:8 and ≥ 1:128

Time frame: 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)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available.

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.

Time frame: From Day 0 to Month 19

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects during the primary phase.

The cut-off value for the hSBA titers was ≥ 1:4 and ≥ 1:8.

Time frame: At Month 5 (one month post-primary for Nimenrix 3+1 and Nimenrix 1+1 Groups)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects for whom data concerning immunogenicity endpoint measures were available. The analysis was performed in a randomized subset of 50% of subjects from each group.

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.

Time frame: Within 8 days (Day 0-7) post booster vaccination

Population: The analysis was performed on the Booster Total Vaccinated cohort, which included all vaccinated subjects at booster time point (at Month 13) who had their symptom sheets completed.

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.

Time frame: Within 8 days (Day 0-7) post primary vaccination

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects during the primary phase who had their symptom sheets completed.

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.

Time frame: Within 8 days (Day 0-7) post booster vaccination

Population: The analysis was performed on the Booster Total Vaccinated cohort, which included all vaccinated subjects at booster time point (at Month 13) who had their symptom sheets completed.

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.

Time frame: Within 8 days (Day 0-7) post primary vaccination

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects during the primary phase who had their symptom sheets completed.

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.

Time frame: Within 31 days (Day 0-30) post booster vaccination

Population: The analysis was performed on the Booster Total Vaccinated cohort, which included all vaccinated subjects at booster time point (at Month 13).

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.

Time frame: Within 31 days (Day 0-30) post each primary vaccine dose

Population: The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects during the primary phase.

Antibody titers are presented as geometric mean titers (GMTs).

Time frame: 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)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available.

Antibody titers are presented as geometric mean titers (GMTs).

Time frame: At Months 5 (one month post-dose 3), 13 (prior booster-dose) and 14 (one month after the booster dose)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity adapted for each timepoint, which included all eligible subjects, who complied with the vaccination schedule and for whom data concerning immunogenicity endpoint measures were available.