A Study of a Quadrivalent Meningococcal Tetanus Protein Conjugate Vaccine in Infants and Toddlers

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.

• Quadrivalent Meningococcal Polysaccharide (A, C, Y, and W-135) Tetanus Protein Conjugate (Biological), also known as TetraMen-T: 0.5 milliliter (mL), Intramuscular (IM) injection
• Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus B Conjugate (Tetanus Toxoid Conjugate) Vaccine Combined (DTaP-IPV/Hib combined) (Biological), also known as Pentacel: 0.5 mL, IM injection
• M-M-RII-Measles, Mumps, and Rubella Virus Vaccine Live (Biological): 0.5 mL, Subcutaneous (SC) injection
• Varicella Virus Vaccine Live (Biological), also known as Varivax: 0.5 mL, SC injection
• Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein) (Biological), also known as Prevnar: 0.5 mL, IM injection
• Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) (Biological), also known as Prevnar 13: 0.5 mL, IM injection
• Rotavirus Vaccine (Biological), also known as RotaTeq/ROTARIX: oral
• Hepatitis B Vaccine (Biological), also known as Engerix-B/Recombivax-HB: 0.5 mL, IM injection

Primary outcomes

• 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) [Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months]: 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.
• 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 [Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months]: 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.
• Percentage of Participants With Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Group 5 - Per-Protocol Population [At the age of 13 months]: 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.
• 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 [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)]: 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.
• 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 [30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)]: 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.
• 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 [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)]: 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.
• 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 [30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)]: 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.
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers (GMTs): Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population [Groups 1, 2, 4, 6, and 7: at the age of 7 months, Group 3: at the age of 5 months]: 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.
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population [Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months]: 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.
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Group 5 - Per-Protocol Population [At the age of 13 months]: Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-HC.
• 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 [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)]: 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.
• Geometric Mean Fold Rise (GMFR) in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population [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)]: 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.
• 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 [Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months]: 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.
• Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population [Groups 1, 3, 4, and 6: at the age of 13 months; Groups 2 and 7: at the age of 16 months]: 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.
• Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Group 5 - Per-Protocol Population [At the age of 13 months]: Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.
• 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 [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)]: 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.
• 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 [30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)]: 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.
• 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 [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)]: 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.
• 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 [30 days post-vaccination at the age of 12 months (i.e. at the age of 13 months)]: 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.
• 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 [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)]: 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.
• Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population [Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months]: 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.
• Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population [Groups 1, 3, 4, and 6: at the age of 13 months; Group 2 and 7: at the age of 16 months]: 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.
• Serum Bactericidal Assay Using Baby Rabbit Complement Geometric Mean Titers in Group 5: Per-Protocol Population [At the age of 13 months]: Meningococcal serogroups A, C, Y, and W-135 antibody titers were measured by SBA-BR.
• 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 [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)]: 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.
• Antibody Titer/Concentration to All the Antigens Contained in Pentacel Vaccines: Groups 1, 2, 4, 6, and 7 - Primary Series Per-Protocol Population [At the age of 7 months]: 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.
• Antibody Titer/Concentration to All Antigens Contained in Pentacel Vaccines: Groups 2 and 7 - Booster Per-Protocol Population [At the age of 16 months]: 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.
• 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 [At the age of 7 months]: 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.
• 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 [At the age of 13 months]: 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.
• 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 [At the age of 13 months]: 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.
• Percentage of Participants With Antibodies to All Antigens Contained in M-M-RII and VARIVAX Vaccines: Groups 1 and 6 - Booster Per-Protocol Population [At the age of 13 months]: 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.
• Geometric Mean Concentrations (GMCs) of Antibody Titers to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population [Groups 1, 2, 4, 6, and 7: at the age of 7 months; Group 3: at the age of 5 months]: 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.
• Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population [Groups 1, 3, 4, and 6: at the age of 13 months, Group 2 and 7: at the age of 16 months]: 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.
• Geometric Mean Concentrations of Antibodies to Tetanus Toxoid: Group 5 - Per-Protocol Population [At the age of 13 months]: Antibody concentrations against tetanus toxoid were measured by ELISA and expressed as GMC.
• Number of Participants With Solicited Injection Site Reactions [Within 7 days post any vaccination]: 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.
• Number of Participants With Solicited Systemic Reactions [Within 7 days post any vaccination]: 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.
• Number of Participants With Unsolicited Adverse Events [Within 30 days post any vaccination]: 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.
• Number of Participants With Immediate Unsolicited AE [Within 30 minutes post any vaccination]: 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.

Sex: All, ages: 42 Days to 365 Days, accepts healthy volunteers

Inclusion Criteria:

* Groups 1, 2, 3, 6, and 7: Aged 42 to 89 days on the day of inclusion; Group 4: Aged 6 months (180 days ± 14 days) on the day of inclusion; Group 5: Aged 12 months (365 days + 14 days) on the day of inclusion.
* Born at full term of pregnancy (greater than or equal to \[≥\] 37 weeks) and with a birth weight ≥2.5 kilogram (kg).
* Informed consent form had been signed and dated by the parent or other legally acceptable representative.
* Participant and parent/guardian were able to attend all scheduled visits and to be complied with all trial procedures.
* Group 4 only: Prior receipt of Pentacel and Prevnar at 2 and 4 months; 1 or 2 doses of rotavirus vaccine; and 2 or 3 previous doses of hepatitis B vaccine.

Group 5 only: Prior receipt of Pentacel and Prevnar at 2, 4, and 6 months; 2 or 3 doses of rotavirus vaccine; and 3 previous doses of hepatitis B vaccine.

Exclusion Criteria:

* Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
* Planned participation in another clinical trial during the present trial period.
* Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
* Planned receipt of any vaccine in the 4 weeks following any trial vaccination, with the exception of influenza vaccine, which may be received 14 days before or after MenACYW Conjugate vaccine.
* Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine.
* Receipt of blood or blood-derived products in the past 30 days, which might interfere with assessment of the immune response.
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks).
* Known personal or maternal seropositivity for human immunodeficiency virus (HIV), hepatitis B vaccine, or hepatitis C, as reported by the parent/guardian.
* History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.
* At high risk for meningococcal infection during the trial.
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
* Thrombocytopenia, as reported by the parent/guardian.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
* History of seizures.
* Personal or family history of Guillain-Barré Syndrome (GBS).
* Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion.

Temporary contraindications were resolved before vaccination:

* Febrile illness (temperature ≥38.0 degree Celsius \[≥100.4 degree Fahrenheit\]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination.
* Group 5 only: Receipt of oral or injected antibiotic therapy within the 72 hours prior to the study blood draw. Topical antibiotics or antibiotic drops were not included in this exclusion criterion. (Note: This did not applied to the other groups at this time, as they did not have a blood draw within 30 days of the initial visit.).

Participant flow

Outcome results

• 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) (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months ; Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 83.1 (72.9 to 90.7); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months ; Group 6: Control: 2, 4, 6, and 12 Months ; Group 7: Control: 2, 4, 6, 12, and 15 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 94.9 (85.9 to 98.9); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 96.4 (87.5 to 99.6); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 100.0 (92.3 to 100.0); Group 6: Control: 2, 4, 6, and 12 Months 28.0 (12.1 to 49.4); Group 7: Control: 2, 4, 6, 12, and 15 Months
• Percentage of Participants With Serum Bactericidal Assay Using Human Complement Titer ≥1:8 and ≥1:4: Group 5 - Per-Protocol Population (Primary), Number, percentage of participants: Group 5: MenACYW Conjugate Vaccine: 12 Months 81.4 (69.1 to 90.3)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 82.6 (61.2 to 95.0); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 85.0 (62.1 to 96.8); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 66.7 (38.4 to 88.2); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 100.0 (71.5 to 100.0)
• 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 (Primary), Number, percentage of participants: Group 5: MenACYW Conjugate Vaccine: 12 Months 33.3 (0.8 to 90.6)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 84.8 (68.1 to 94.9); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 85.7 (71.5 to 94.6); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 92.1 (78.6 to 98.3); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 97.0 (84.2 to 99.9)
• 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 (Primary), Number, percentage of participants: Group 5: MenACYW Conjugate Vaccine: 12 Months 60.0 (45.9 to 73.0)
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers (GMTs): Groups 1, 2, 3, 4, 6, and 7 - Primary Series Per-Protocol Population (Primary), Geometric mean, titers (1/dilution): Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months ; Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 16.3 (11.9 to 22.2); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months ; Group 6: Control: 2, 4, 6, and 12 Months ; Group 7: Control: 2, 4, 6, 12, and 15 Months
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Groups 1, 2, 3, 4, 6, and 7 - Booster Per-Protocol Population (Primary), Geometric mean, titers (1/dilution): Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 58.9 (39.9 to 87.2); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 98.2 (66.1 to 145.9); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 151.1 (102.2 to 223.4); Group 6: Control: 2, 4, 6, and 12 Months 2.7 (2.1 to 3.4); Group 7: Control: 2, 4, 6, 12, and 15 Months
• Serum Bactericidal Assay Using Human Complement Geometric Mean Titers: Group 5 - Per-Protocol Population (Primary), Geometric mean, titers (1/dilution): Group 5: MenACYW Conjugate Vaccine: 12 Months 13.1 (9.5 to 18.1)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 83.9 (71.7 to 92.4); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 85.5 (74.2 to 93.1); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 84.9 (72.4 to 93.3); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 97.7 (88.0 to 99.9)
• Geometric Mean Fold Rise (GMFR) in SBA-HC Titer After the Booster Vaccination: Groups 1, 2, 3, and 4 - Booster Per-Protocol Population (Primary), Geometric mean, fold rise: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 8.3 (5.8 to 11.8); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 12.0 (8.0 to 18.0); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 16.9 (10.9 to 26.0); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 24.5 (17.4 to 34.5)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months ; Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 52.6 (40.8 to 64.2); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months ; Group 6: Control: 2, 4, 6, and 12 Months ; Group 7: Control: 2, 4, 6, 12, and 15 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 80.4 (67.6 to 89.8); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months ; Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 96.1 (86.5 to 99.5); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 95.2 (83.8 to 99.4); Group 6: Control: 2, 4, 6, and 12 Months 8.3 (1.0 to 27.0); Group 7: Control: 2, 4, 6, 12, and 15 Months
• Percentage of Participants With SBA-BR Titer ≥1:8 and ≥1:128: Group 5 - Per-Protocol Population (Primary), Number, percentage of participants: Group 5: MenACYW Conjugate Vaccine: 12 Months 62.1 (48.4 to 74.5)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 100.0 (29.2 to 100.0); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 100.0 (47.8 to 100.0); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 33.3 (4.3 to 77.7); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 66.7 (22.3 to 95.7)
• 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 (Primary), Number, percentage of participants
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 78.0 (64.0 to 88.5); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 79.2 (65.0 to 89.5); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 95.5 (84.5 to 99.4); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 93.8 (79.2 to 99.2)
• 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 (Primary), Number, percentage of participants: Group 5: MenACYW Conjugate Vaccine: 12 Months 61.8 (47.7 to 74.6)
• 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 (Primary), Number, percentage of participants: Group 1: MenACYW Conjugate Vaccine: 2, 4, 6, and 12 Months 79.2 (65.9 to 89.2); Group 2: MenACYW Conjugate Vaccine: 2, 4, 6, and 15 Months 81.1 (68.0 to 90.6); Group 3: MenACYW Conjugate Vaccine: 2, 4, and 12 Months 88.0 (75.7 to 95.5); Group 4: MenACYW Conjugate Vaccine: 6 and 12 Months 89.5 (75.2 to 97.1)
• 17 more outcome measures not shown.

Adverse events

Time frame: Unsolicited non-serious AEs were collected from Day 0 to Day 30 post any vaccination. SRs were collected within 7 days post any vaccination. Serious adverse events were collected throughout the trial (up to the age of 13 months for Groups 1, 3, 4, 5 and 6; up to the age of 16 months for Groups 2 and 7), i.e. 30 days after last vaccination.

Serious adverse events by term

Other adverse events by term

• Results publication: Cornish MJ, Hedrick JA, Gabrielsen AA, Johnson AD, Miriam Pina L, Rehm C, Pan J, Neveu D, Da Costa X, Jordanov E, Dhingra MS. Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study. Vaccine. 2022 Mar 1;40(10):1421-1438. doi: 10.1016/j.vaccine.2022.01.050. Epub 2022 Feb 7. PMID 35144847

• Medical Director, Study director, Sanofi Pasteur Inc.