The purpose of this study was to evaluate the optimal vaccination schedule for a Quadrivalent Meningococcal Polysaccharide (A, C, Y and W-135) Tetanus Protein Conjugate Vaccine (MenACYW Conjugate vaccine) in order to provide an effective protein conjugate quadrivalent meningococcal vaccine in the population with the highest incidence of disease. Objectives: * To describe the safety profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations. * To describe the immunogenicity profile of MenACYW Conjugate vaccine administered at 5 different schedules and concomitantly with routine pediatric vaccinations. * To describe the immunogenicity profiles of selected licensed pediatric vaccines (Pentacel, Prevnar, M-M-RII, and Varivax) when administered either concomitantly with or without MenACYW Conjugate vaccine.
Participants received study vaccinations beginning at age 2, 6, 12, or 15 months, depending on the assigned schedule in their randomized groups. All participants underwent safety and immunogenicity assessments according to the schedule for their assigned group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
580
0.5 milliliter (mL), Intramuscular (IM) injection
0.5 mL, IM injection
0.5 mL, Subcutaneous (SC) injection
0.5 mL, SC injection
0.5 mL, IM injection
0.5 mL, IM injection
oral
0.5 mL, IM injection
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Tuscaloosa, Alabama, United States
Unnamed facility
Jonesboro, Arkansas, United States
Unnamed facility
Little Rock, Arkansas, United States
Unnamed facility
Fountain Valley, California, United States
Unnamed facility
Huntington Beach, California, United States
Unnamed facility
Marietta, Georgia, United States
Unnamed facility
Woodstock, Georgia, United States
Unnamed facility
Bardstown, Kentucky, United States
Unnamed facility
Crestview Hills, Kentucky, United States
...and 15 more locations
Percentage of Participants With an Serum Bactericidal Assay (SBA) Using Human Complement (SBA-HC) Titer Greater or Than Equal to (≥) 1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-protocol Population (PPP)
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. The PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not receive the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provide a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Percentage of Participants With an Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not received the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provided a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Percentage of Participants With Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. PPP consisted of all participants included in the trial who received at least one dose of study or control vaccine, excluding those who did not meet all protocol-specified inclusion/exclusion criteria, did not received the correct number of doses of the investigational vaccine, received a vaccine other than the one that he/she was randomized to receive, did not provided a post-dose serology sample in the proper time window, received a protocol-restricted therapy, medication or vaccine, was on systemic antibiotics within 3 days prior to study blood draw, had no serology sample or did not produce at least one valid test result, did not receive vaccine in the proper time window.
Time frame: At the age of 13 months
Percentage of Participants With SBA-HC Pre-booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-booster titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-booster titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-HC Pre-vaccination Titer ≥1:8 Who Then Achieved ≥4-fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-vaccination titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-vaccination titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post-vaccination) were reported.
Time frame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With SBA-HC Pre-booster Titer Less Than (<) 1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC After Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Pre-booster titer was defined as titer values reported before the age of 12 months. Percentage of participants whose pre-booster titer was \<1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-HC Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-HC Titer After Vaccination: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Percentage of participants with pre-vaccination titer \<1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post vaccination) were reported.
Time frame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers (GMTs): Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: Groups 1, 2, 4, 6, and 7: at the age of 7 months, Group 3: at the age of 5 months
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC.
Time frame: At the age of 13 months
Percentage of Participants With ≥4-fold Rise in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Percentage of participants with ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Geometric Mean Fold Rise (GMFR) in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3 and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months), Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With a Serum Bactericidal Assay Using Baby Rabbit Complement (SBA-BR) Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months
Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.
Time frame: At the age of 13 months
Percentage of Participants With SBA-BR Pre-Booster Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-booster titer was defined as titer value reported before the age of 12 months. Percentage of participants whose pre-booster titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-BR Pre-Vaccination Titer ≥1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants whose pre-vaccination titer was ≥1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer at the age of Month 13 (i.e. 30-days post vaccination at Month 12) were reported.
Time frame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With SBA-BR Pre-Booster Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titers After Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-booster titer was defined as titer value reported before the age of 12 months. Percentage of participants whose pre-booster titer was \<1:8 and achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months); Group 2: 30 days post-vaccination at the age of 15 months (i.e. at the age of 16 months)
Percentage of Participants With SBA-BR Pre-Vaccination Titer <1:8 Who Then Achieved ≥4-Fold Rise in SBA-BR Titer After Vaccination: Group 5 - Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Pre-vaccination titer was defined as titer value reported before the age of 12 months. Percentage of participants with pre-vaccination titer \<1:8 and who achieved ≥4-fold rise in each meningococcal serogroups antibody titer (30 days post-vaccination) were reported.
Time frame: 30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)
Percentage of Participants With ≥4-fold Rise in SBA-BR Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants with ≥4-fold rise in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP which was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post booster vaccination (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination (i.e., at the age of 16 months)
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, 4, and 6: at the age of 13 months; Group 2 and 7: at the age of 16 months
Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers in Group 5: Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.
Time frame: At the age of 13 months
Geometric Mean Fold Rise in Serum Bactericidal Assay Using Baby Rabbit Complement Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population
Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR. Percentage of participants with GMFR in each meningococcal serogroups antibody titer (30-days post booster vaccination) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: Groups 1, 3, and 4: 30 days post booster vaccination at the age of 12 months (i.e., at the age of 13 months); Group 2: 30 days post booster vaccination at the age of 15 months (i.e. at the age of 16 months)
Antibody Titer/Concentration to All the Antigens Contained in Pentacel Vaccines: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population
Pentacel vaccine is Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined). Antibody titer to all antigens contained in pentacel vaccines (i.e., Anti-PRP, Anti-Diptheria, Anti-pertussis \[pertussis toxoid \[PT\], pertactin \[PRN\], filamentous hemagglutinin \[FHA\], and fimbriae \[FIM\]\], Anti-poliovirus \[anti-poliovirus Type 1, Type 2 and Type 3\] and anti-tetanus) were reported. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: At the age of 7 months
Antibody Titer/Concentration to All Antigens Contained in Pentacel Vaccines: Groups 2 and 7 - Booster Per-Protocol Population
Pentacel vaccine is Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined). Antibody titer to all antigens contained in pentacel vaccines (i.e., Anti-PRP, Anti-Diptheria, Anti-pertussis \[PT, PRN, FHA, and FIM\], Anti-poliovirus \[anti-poliovirus Type 1, Type 2, and Type 3\], and Anti-tetanus) were reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: At the age of 16 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population
Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F, and 23F is reported. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age.
Time frame: At the age of 7 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Groups 1, 3, 4, and 6 - Booster Series Per-Protocol Population
Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL and ≥1.0 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F and 23F is reported. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: At the age of 13 months
Percentage of Participants With Antibody Concentration ≥0.35 μg/mL and ≥1.0 μg/mL for Serotypes in Prevnar 7 or 13 Vaccine: Group 5- Per-Protocol Population
Percentage of participants with anti-pneumococcal antibody concentrations ≥0.35 μg/mL and ≥1.0 μg/mL for serotypes in Prevnar 7 or 13 vaccine i.e. 4, 6B, 9V, 14, 18C, 19F and 23F is reported.
Time frame: At the age of 13 months
Percentage of Participants With Antibodies to All Antigens Contained in M-M-RII and VARIVAX Vaccines: Groups 1 and 6 - Booster Per-Protocol Population
Antibodies responses were measured by ELISA. Antigens contained in M-M-RII: Measles, Mumps, and Rubella and in Varivax®: Varicella. Percentage of participants with anti-measles, anti-mumps, anti-rubella, and anti-varicella antibody concentration that met the respective mentioned criterion were reported: Measles: ≥255 milli-International Units per milliliter (mIU/mL); Mumps: ≥10 Antibody units per milliliter (AbU/mL); Rubella: ≥10 International Units per milliliter (IU/mL); Varicella: ≥5 glycoprotein based enzyme-linked immunosorbent assay (gpELISA) unit/mL. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months.
Time frame: At the age of 13 months
Geometric Mean Concentrations (GMCs) of Antibody Titers to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population
Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC. Primary series PPP was defined as the PPP which was used for reporting data of time points prior to 12 months of age. Here, '0' in number analyzed field signifies none of the participants were evaluable at that specified time point because different groups had different planned data collection time points as defined in time frame and pre-specified in protocol.
Time frame: Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months
Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population
Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC. Booster PPP was defined as the PPP that was used for reporting data of time points at and after the age of 12 months. Here, '0' in number analyzed field signifies none of the participants were evaluable at that specified time point because different groups had different planned data collection time points as defined in time frame and pre-specified in protocol.
Time frame: Groups 1, 3, 4, and 6: at the age of 13 months, Group 2 and 7: at the age of 16 months
Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Group 5 - Per-Protocol Population
Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC.
Time frame: At the age of 13 months
Number of Participants With Solicited Injection Site Reactions
Solicited injection site reactions: tenderness/pain, erythema, and swelling and were planned to be collected and reported for each vaccine separately and not planned to be collected for Rotavirus vaccine. Here, '0' in number analyzed field for MenACYW categories signifies no participant were evaluable because in Groups 6 and 7 MenACYW vaccine was not administered; for Group 5, '0' in number analyzed field signifies safety data collection was not planned for Pentacel and Hepatitis-B vaccines; for Groups 2 and 7, '0' in number analyzed field signifies safety data collection was not planned for M-M-RII and VARIVAX vaccines, as pre-specified.
Time frame: Within 7 days post any vaccination
Number of Participants With Solicited Systemic Reactions
An solicited reaction (SR) was an adverse reaction (AR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the electronic case report form (eCRF). Systemic AEs were all AEs that were not injection site reactions. They, therefore, include systemic manifestations as well as localized or topical manifestations that were not associated with the vaccination site. Solicited systemic reactions included Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability.
Time frame: Within 7 days post any vaccination
Number of Participants With Unsolicited Adverse Events
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination. These included both serious and non-serious events.
Time frame: Within 30 days post any vaccination
Number of Participants With Immediate Unsolicited AE
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination. These included both serious and non-serious events. Immediate Unsolicited AE were AEs reported within 30 minutes of vaccine administration.
Time frame: Within 30 minutes post any vaccination
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