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

Sanofi Pasteur, a Sanofi Company463 enrolled

Overview

Primary Objective: To demonstrate the non-inferiority of the seroprotection rate (serum bactericidal assay using human complement \[hSBA\] titer greater than or equal to \[\>=\] 1:8) to meningococcal serogroups A, C, W, and Y following the administration of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate vaccine (MenACYW Conjugate vaccine) (Group 1) compared to a single dose of Nimenrix® (Group 2). Secondary Objective: To describe: * the antibody response of meningococcal serogroups A, C, W, and Y measured by hSBA, before and 1 month following meningococcal vaccination administered alone (Groups 1 and 2) or concomitantly with 9-valent human papilloma virus (9vHPV) and tetanus, diphtheria, and acellular pertussis - inactivated polio vaccine \[adsorbed, reduced antigen(s) content\] (Tdap-IPV) vaccines (Group 3). * the antibody response of meningococcal serogroup C measured by hSBA and serum bactericidal assay using baby rabbit complement (rSBA), before vaccination and at Day 31 after vaccination with MenACYW Conjugate vaccine or Nimenrix® (Groups 1 and 2) according to MenC primed status. * the antibody response against antigens of 9vHPV and Tdap-IPV vaccines, before and 1 month following vaccination. * the safety profile in each group after each and any vaccination.

The duration of study participation for each participant was approximately 30 to 60 days, including 2 or 3 visits (1 or 2 vaccination visit) and 1 or 2 telephone calls, depending on study Group. \* This was the first dose of 9vHPV, of the 2-dose or 3-dose series according to the local recommendations and age of the participant. These additional vaccinations for the completion of 9vHPV schedule took place outside of the objectives and scope of this study and thus were not described in this protocol.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Aged 10 to 17 years on the day of inclusion ('10 to 17 years' means from the day of the 10th birthday to the day before the 18th birthday). * Meningococcal serogroup C Conjugate vaccine (MenC) naïve participants or participants having received monovalent MenC priming in infancy (less than \[\<\] 2 years of age). * Assent form had been signed and dated by the participant as per local regulation, and Informed Consent Form had been signed and dated by the parent/legally acceptable representative and by the participant if she/he turns 18 years old during the study. * Participants and parent/legally acceptable representative were able to attend all scheduled visits and compiled with all study procedures. * Covered by health insurance, if required by local regulations. Exclusion Criteria: * Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after last vaccination. To be considered of non-childbearing potential, a female must be pre-menarche. * Previous vaccination against meningococcal disease with either the study vaccine or another vaccine (i.e., polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, W, or Y; or meningococcal B serogroup-containing vaccine), except licensed monovalent MenC vaccination received before 2 years of age. * Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. * Receipt of any vaccine in the 4 weeks preceding any study vaccination or planned receipt of any vaccine in the 4 weeks following any study vaccination except for influenza vaccination, which might receive at least 2 weeks before study vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines. * History of vaccination with any tetanus, diphtheria, pertussis, or inactivated polio virus vaccine within the previous 3 years. * Previous human papilloma virus (HPV) vaccination. * Receipt of immune globulins, blood or blood-derived products in the past 3 months. * Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). * History of meningococcal infection, confirmed either clinically, serologically, or microbiologically. * Known history of diphtheria, tetanus, pertussis, poliomyelitis, and/or HPV infection or disease. * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances. * Personal history of Guillain-Barré syndrome. * Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within at least 10 years of the proposed study vaccination. * Personal history of new or past encephalopathy, progressive or unstable neurological disorder, or unstable epilepsy. * Verbal report of thrombocytopenia, contraindicating intramuscular vaccination. * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination. * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. * Current alcohol abuse or drug addiction. * Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion. * Moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination or febrile illness (temperature \>= 38.0 degree Celsius \[\>= 100.4 degree Fahrenheit\]). A prospective participant should not be included in the study until the condition had resolved or the febrile event has subsided. * Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw. * Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study. * Participant at high risk for meningococcal infection during the study (specifically but not limited to participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (23)

Investigational Site Number :3480003

Budapest, Hungary

Investigational Site Number :3480001

Győr, Hungary

Investigational Site Number :3480002

Miskolc, Hungary

Investigational Site Number :3480004

Szigetvár, Hungary

Investigational Site Number :3480006

Szombathely, Hungary

Investigational Site Number :3800005

Foggia, Apulia, Italy

Investigational Site Number :3800006

Catanzaro, Calabria, Italy

Investigational Site Number :3800002

Milan, Lombardy, Italy

Investigational Site Number :3800004

Palermo, Sicily, Italy

Investigational Site Number :3800001

Genova, Italy

...and 13 more locations

Outcomes

Primary Outcomes

Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, W, and Y Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® Vaccine (Non-inferiority Analysis): Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination)

Secondary Outcomes

Geometric Mean Titers (GMTs) of Antibodies Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W

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

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Percentage of Participants With hSBA Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Percentage of Participants With >= 4-Fold Rise In hSBA Antibody Titers Against Meningococcal Serogroups A, C, Y, and W

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.

Time frame: From Baseline (Day 01) to Day 31 (post-vaccination)

Percentage of Participants With Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W

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.

Time frame: Day 31 (post-vaccination)

Geometric Mean Titers (GMTs) of Antibodies Measured by hSBA Against Meningococcal Serogroup C: Meningococcal Serogroup C Conjugate Vaccine (MenC) Primed Participants in Groups 1 and 2

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Titers (GMTs) of Antibodies Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Against Meningococcal Serogroups C: Meningococcal Serogroup C Conjugate Vaccine (MenC) Primed Participants in Groups 1 and 2

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Diphtheria, Tetanus Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Polio Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Diphtheria, Tetanus Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Polio Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Concentrations (GMCs) of Anti-Pertussis Antibodies Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Concentrations Ratios (GMCRs) of Antibodies Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Concentrations Ratios (GMCRs) of Antibodies Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine: Group 3

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Percentage of Participants With Antibody Titers Above Predefined Thresholds Against Antigens Contained in Tetanus, Diphtheria, and Acellular Pertussis - Inactivated Polio Vaccine (Tdap-IPV) Vaccine in Groups 1 and 2

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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Percentage of Participants With Vaccine Seroresponse Against Pertussis Antigens

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.

Time frame: Day 61 (post-vaccination for Groups 1 and 2) and Day 31 (post-vaccination for Group 3)

Geometric Mean Titers (GMTs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine in 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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Titers (GMTs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine: Group 3

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Geometric Mean Titers Ratios (GMTRs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine in 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. 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.

Time frame: Day 31 (post-vaccination) and Day 61 (post-vaccination)

Geometric Mean Titers Ratios (GMTRs) of Antibodies Against Antigens Contained in Human Papillomavirus (HPV) Vaccine: Group 3

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.

Time frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination)

Percentage of Participants With Vaccine Seroconversion Against Antigens Contained in Human Papillomavirus (HPV) Vaccine

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.

Time frame: Day 61 (post-vaccination for Groups 1 and 2) and Day 31 (post-vaccination for Group 3)

Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)

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.

Time frame: Within 30 minutes post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])

Number of Participants Reporting Solicited Injection Site Reactions

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.

Time frame: Within 7 days post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])

Number of Participants Reporting Solicited Systemic Reactions

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.

Time frame: Within 7 days post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])

Number of Participants Reporting Unsolicited Adverse Events (AEs)

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.

Time frame: From Day 01 up to Day 31 post-any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 31])

Number of Participants Reporting Serious Adverse Events (SAEs) Including Adverse Events of Special Interest (AESI)

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.

Time frame: From Day 01 up to the last study day (i.e., Day 61 for Groups 1 and 2 and Day 31 for Group 3)

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

Overview

Conditions

Interventions

Eligibility

Locations (23)

Outcomes

Primary Outcomes

Secondary Outcomes