Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Compared to a Meningococcal Reference Vaccine, and When Given Alone or With Two Other Vaccines in Healthy Adolescents

Antibody titers against meningococcal serogroups A, C, W, and Y were measured by serum bactericidal assay using human complement (hSBA). Non-inferiority data analysis for this outcome measure was planned to be conducted only for Groups 1 and 2, not for Group 3. Group 3 data is reported separately.

GMTs against Meningococcal Serogroups A, C, Y, and W were measured by hSBA. Titers were expressed in terms of 1/dilution.

Antibody titers against Meningococcal Serogroups A, C, Y and W were measured by hSBA. Percentage of participants With hSBA antibody titers >=1:4 and >=1:8 for serogroups A, C, Y, and W were reported in the outcome measure.

Antibody titers against Meningococcal Serogroups A, C, Y and W were measured by hSBA. Fold-rise was calculated as ratio of post-dose titer on Day 31 to pre-dose titer on Day 01.

Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The vaccine seroresponse was defined as a post-vaccination hSBA titer greater than or equal to (>=) 1:16 for participants with pre-vaccination hSBA titer less than (<) 1:8, or a >= 4-fold increase in hSBA titer from pre-vaccination to post-vaccination for participants with pre-vaccination hSBA titer >= 1:8.

GMTs against meningococcal Serogroup C in MenC primed participants (participants who received monovalent MenC priming in infancy < 2 years of age) were measured by hSBA. Titers were expressed in terms of 1/dilution.

GMTs against Serogroup C in MenC primed participants (participants who received monovalent MenC priming in infancy < 2 years of age) were measured by rSBA. Titers were expressed in terms of 1/dilution.

Geometric mean concentrations of anti-Diphtheria, and tetanus antibodies were measured by electro chemiluminescent method. Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

GMCs of anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. Concentrations were expressed in terms of titers (1/dilution). Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

GMCs of anti-pertussis antibodies (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN]) and fimbriae types 2 and 3 [FIM], were measured by electro chemiluminescent method. Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

GMCs of anti-diphtheria, and tetanus antibodies were measured by electro chemiluminescent method. Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

GMCs of anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. Concentrations were expressed in terms of titers (1/dilution). Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

GMCs of anti-pertussis antibodies (PT, FHA, FIM, and PRN) antibodies were measured by electro chemiluminescent method. Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

Anti-Diphtheria, Tetanus, and Pertussis (PT, FHA, FIM, and PRN) antibodies were measured by electro chemiluminescent method. Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. GMCRs were calculated as the ratio of GMCs at Day 61 and Day 31. Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

Anti-Diphtheria, Tetanus, and Pertussis (PT, FHA, FIM, and PRN) antibodies were measured by electro chemiluminescent method. Anti-poliovirus types 1, 2, and 3 were measured by neutralization assay. GMCRs were calculated as the ratio of GMCs at Day 31/Day 01. Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

Antibody titers above predefined thresholds against Tdap-IPV vaccine antigens were defined as: Anti-D Ab titers and Anti-T Ab titers >= 0.1 IU/mL, and >= 1.0 IU/mL; Anti-Polio 1, 2, and 3 Ab titers >= 8 (1/dilution). Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

Antibody titers above predefined thresholds against Tdap-IPV vaccine antigens were defined as: Anti-D Ab titers and Anti-T Ab titers >= 0.1 IU/mL, and >= 1.0 IU/mL; Anti-Polio 1, 2, and 3 Ab titers >= 8 (1/dilution). Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

Vaccine seroresponse was defined as post-vaccination concentration >= 4 * Baseline concentration, if the anti-pertussis antibody concentration at Baseline was < 4*lower limit of quantification (LLOQ), or >= 2*Baseline concentration, if the anti-pertussis antibody concentration at Baseline was >= 4*LLOQ. Post vaccine seroresponse for anti-pertussis antigens was Day 31 for Group 3 and Day 61 for Groups 1 and 2.

Anti-HPV antibodies were measured by the direct virus-like particle (VLP) electrochemiluminescence multi-plex immunoassay for detection of antibodies towards HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Titers were expressed in terms of 1/dilution. Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

Anti-HPV antibodies were measured by the direct VLP electrochemiluminescence multi-plex immunoassay for detection of antibodies towards HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Titers were expressed in terms of 1/dilution. Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

Anti-HPV antibodies were measured by the direct virus-like particle (VLP) electrochemiluminescence multi-plex immunoassay for detection of antibodies towards HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. GMTRs were calculated as the ratio of GMTs at Day 61/Day 31. Blood samples were assessed for participants at Day 31 and at Day 61, respectively.

Anti-HPV antibodies were measured by the direct VLP electrochemiluminescence multi-plex immunoassay for detection of antibodies towards HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. GMTRs were calculated as the ratio of GMTs at Day 31/Day 01. Blood samples were assessed for participants at Day 01 and at Day 31, respectively.

Vaccine Seroconversion was defined as changing serostatus from seronegative (participants with a titer inferior to the serostatus cut-off value) at Baseline to seropositive after vaccination. A participant with a titer at or above the serostatus cut-off for a given HPV type was considered seropositive for that type. The serostatus cut-offs for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were 9, 6, 5, 5, 3, 4, 3, 5 and 5 milli-Merck units (mMU)/mL, respectively. Post vaccine seroconversion for antigens contained in HPV vaccine was Day 31 for Group 3 and Day 61 for Groups 1 and 2.

An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report form (CRF) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. Reported AEs for each arm were presented as pre-specified in the study protocol.

SR: expected AR (sign or symptom) observed & reported under conditions (nature & onset) prelisted (i.e., solicited) in CRF & considered as related to product. Injection site reactions: pain, erythema, & swelling. Here, "0" in number analyzed for MenACYW categories signifies no participant were evaluable as in Group (Gps.) 2 MenACYW vaccine was not administered; for Gps.1& 3: "0" in number analyzed for Nimenrix signifies no participant were evaluable as in Gps. 1 & 3 Nimenrix was not administered. At Vaccination (vacc.)1 (Gps.1 & 2): "0" in number analyzed for 9vHPV & Tadp-IPV signifies no participant were evaluable as these vaccines were not administered at vacc.1 (Day01). At Vacc. 2 (Gps.1, 2 & 3): "0" in number analyzed for MenACYW and Nimenrix signifies no participant were evaluable as these vaccines were not administered at vacc. 2 (Day 31); & for Gps. 3 "0" in number analyzed for 9vHPV and Tadp-IPV signifies no participant were evaluable as these vaccines were not administered.

A solicited reaction (SR) was an expected adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRF and considered as related to the product administered. Solicited systemic reactions included fever, headache, malaise, and myalgia. Reported AEs for each arm were presented as pre-specified in the study protocol.

An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Reported AEs for each arm were presented as pre-specified in the study protocol.

A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. A SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as event for which ongoing monitoring and rapid communication by the investigator to the sponsor was done. Reported AEs for each arm were presented as pre-specified in the study protocol.