Meningitis, Meningococcal Infections, Meningococcal Meningitis
Conditions
Keywords
Meningitis, Meningococcal Meningitis, MenACYW Conjugate vaccine, MENVEO vaccine, Adacel®, GARDASIL®
Brief summary
The purpose of the study was to evaluate the immunogenicity and describe the safety of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed vaccine MENVEO® in adolescents 10 to 17 years of age in the United States (US). This study also evaluated the immunogenicity and safety of MenACYW Conjugate vaccine when given alone compared to when given concomitantly with tetanus, diphtheria, acellular pertussis (Tdap) vaccine and human papilloma virus (HPV) vaccine. Primary objective: * To evaluate the antibody responses to the antigens present in MenACYW Conjugate vaccine when MenACYW Conjugate vaccine was given alone compared to those when MENVEO vaccine was given alone. Secondary objective: * To evaluate the antibody responses to the antigens present in MenACYW Conjugate vaccine, when MenACYW Conjugate vaccine was given concomitantly with Tdap and HPV vaccines, compared to those when it was given alone. * To evaluate the antibody responses to the antigens present in Tdap vaccine, when Tdap vaccine was given concomitantly with MenACYW Conjugate vaccine and HPV vaccine, compared to those when Tdap vaccine was given with HPV vaccine only. * To evaluate the antibody responses to the antigens present in HPV vaccine after the 3-dose series, when the first dose of HPV vaccine is given concomitantly with MenACYW Conjugate vaccine and Tdap vaccine, compared to those when the first dose of HPV vaccine is given with Tdap vaccine only. Observational objective: * To describe the safety profile of MenACYW Conjugate vaccine, compared to that of the licensed vaccine MENVEO®, and when MenACYW Conjugate vaccine was given with Tdap and HPV vaccines.
Detailed description
Healthy adolescents were randomized and received a single dose of their assigned vaccines. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.
Interventions
BIOLOGICALMeningococcal Polysaccharide (Serogroups A, C, Y, and W135) Tetanus Toxoid Conjugate Vaccine
0.5 milliliter (mL), Intramuscular (IM)
BIOLOGICALMeningococcal (Groups A, C, Y and W135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
0.5 mL, IM
BIOLOGICALAdacel®: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed
0.5 mL, IM
BIOLOGICALGARDASIL®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant
0.5 mL, IM
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 10 to 17 years on the day of inclusion. * Informed consent form was signed and dated by the parent(s) or another legally acceptable representative. * Assent form was signed and dated by the participant. * Participant and parent legally acceptable representative were able to attend all scheduled visits and comply with all trial procedures.
Exclusion criteria
* Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination). * Participation in the 4 weeks preceding the first trial vaccination(s) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. * Receipt of any vaccine in the 4 weeks preceding the first trial vaccination(s) or planned receipt of any vaccine in the 4 weeks prior to or following any trial vaccination except for influenza vaccination, which may be received at least 2 weeks before or after any study vaccines. This exception included monovalent influenza vaccines and multivalent influenza vaccines. * Previous vaccination against meningococcal disease with either the trial vaccine or any mono- or polyvalent polysaccharide or conjugate meningococcal vaccine containing A, C, W, or Y antigens. * History of vaccination with any tetanus, diphtheria, or pertussis vaccine within the previous 4 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. * At high risk for meningococcal infection during the trial (i.e., participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease). * 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, including encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous pertussis antigen-containing vaccine. * 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. * 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 (e.g., human immunodeficiency virus \[HIV\] hepatitis B, hepatitis C) that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion. * Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature \>= 100.4 degree fahrenheit \[°F\]). A prospective participant was not included in the study until the condition had resolved or the febrile event had 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., natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Day 30 (post-vaccination) | Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers greater than or equal to (\>=) 1:8 for participants with pre-vaccination hSBA titers less than (\<) 1:8 or at least a 4-fold increase in hSBA titers from pre- to post vaccination for participants with pre-vaccination hSBA titers \>= 1:8. Data for this outcome measure was not planned to be collected and analyzed for Group 4:Tdap+HPV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Day 30 (post-vaccination on Day 0) | Anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN), and Fimbriae types 2 and 3 (FIM) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). |
| Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Day 30 (post-vaccination on Day 0) | Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus antibodies were measured by ELISA. |
| Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Day 210 (post-vaccination on Day 0) | Anti-HPV 6, 11, 16, and 18 antibodies were measured using a competitive Luminex immunoassay. Seroconversion was defined as changing serostatus from seronegative to seropositive. Cutoff values for HPV seropositivity were \>= 20 milli-Merck units per milliliter (mMU/mL) for types 6 and 16, \>= 16 mMU/mL for type 11, and \>= 24mMU/mL for type 18. |
| Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Day 30 (post-vaccination on Day 0) | Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers \>= 1:8 for participants with pre-vaccination hSBA titers \< 1:8 or at least a 4-fold increase in hSBA titers from pre- to post vaccination for participants with pre-vaccination hSBA titers \>= 1:8. |
| Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | Within 7 days after vaccines injections at Day 0 | A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling. |
| Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | Within 7 days after vaccines injections at Day 0 | A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling. |
| Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Within 7 days after vaccines injections at Day 0 | A Solicited Reaction (SR) was an Adverse Event (AE) that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Study participants were enrolled in 40 centers in the Unites States (US) from 22 July 2014 to 25 February 2015.
Pre-assignment details
A total of 1715 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: MenACYW Conjugate Vaccine Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MenACYW Conjugate vaccine on Day 0. | 505 |
| Group 2: MENVEO® Vaccine Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MENVEO® vaccine on Day 0. | 507 |
| Group 3: MenACYW Conjugate Vaccine+Tdap+HPV Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of MenACYW Conjugate vaccine, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap), and Dose 1 of HPV Vaccine on Day 0. HPV Vaccine Dose 2 and Dose 3 were given at 2 and 6 months, respectively, after Dose 1 given on Day 0. | 403 |
| Group 4: Tdap+HPV Healthy, meningococcal-vaccine naïve participants aged 10 to 17 years received a single dose of Tdap and Dose 1 of HPV Vaccine on Day 0. HPV Vaccine Dose 2 and Dose 3 were given at 2 and 6 months, respectively, after Dose 1 given on Day 0. | 300 |
| Total | 1,715 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 | 9 | 10 |
| Overall Study | Protocol Violation | 3 | 3 | 6 | 7 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 12 | 13 |
Baseline characteristics
| Characteristic | Group 1: MenACYW Conjugate Vaccine | Total | Group 4: Tdap+HPV | Group 3: MenACYW Conjugate Vaccine+Tdap+HPV | Group 2: MENVEO® Vaccine |
|---|---|---|---|---|---|
| Age, Continuous | 11.4 years STANDARD_DEVIATION 1.39 | 11.4 years STANDARD_DEVIATION 1.32 | 11.4 years STANDARD_DEVIATION 1.41 | 11.3 years STANDARD_DEVIATION 1.06 | 11.4 years STANDARD_DEVIATION 1.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 8 Participants | 1 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 8 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 85 Participants | 18 Participants | 15 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 26 Participants | 82 Participants | 12 Participants | 20 Participants | 24 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 10 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 442 Participants | 1520 Participants | 261 Participants | 361 Participants | 456 Participants |
| Region of Enrollment United States | 505 Participants | 1715 Participants | 300 Participants | 403 Participants | 507 Participants |
| Sex: Female, Male Female | 259 Participants | 832 Participants | 144 Participants | 197 Participants | 232 Participants |
| Sex: Female, Male Male | 246 Participants | 883 Participants | 156 Participants | 206 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 503 | 0 / 501 | 0 / 392 | 0 / 296 |
| other Total, other adverse events | 331 / 503 | 337 / 501 | 348 / 392 | 263 / 296 |
| serious Total, serious adverse events | 4 / 503 | 4 / 501 | 4 / 392 | 4 / 296 |
Outcome results
Primary
Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine
Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers greater than or equal to (\>=) 1:8 for participants with pre-vaccination hSBA titers less than (\<) 1:8 or at least a 4-fold increase in hSBA titers from pre- to post vaccination for participants with pre-vaccination hSBA titers \>= 1:8. Data for this outcome measure was not planned to be collected and analyzed for Group 4:Tdap+HPV.
Time frame: Day 30 (post-vaccination)
Population: Analysis was performed on Per-Protocol Analysis Set-1(PPAS-1) defined for accessing the ACYW \& Tdap immune response data for all participants after they had received vaccination(s) at Visit 1(Day 0) \& completed blood sampling (BL) at Visit 2(Day 30). Here 'Number analyzed' signifies number of participants with available data for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup A | 75.6 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup C | 97.2 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup Y | 97.0 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup W | 86.2 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup W | 66.6 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup A | 66.4 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup Y | 80.8 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Vaccine Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Serogroup C | 72.6 percentage of participants |
Comparison: Serogroup A95% CI: [3.4, 15]
Comparison: Serogroup C95% CI: [20.3, 29]
95% CI: [12.3, 20.2]
Comparison: Serogroup W95% CI: [14.2, 24.8]
Secondary
Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines
Anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN), and Fimbriae types 2 and 3 (FIM) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 30 (post-vaccination on Day 0)
Population: Analysis was performed on PPAS-1. Here 'Number analyzed' signifies number of participants with available data for specified category. Data for this outcome measure was not planned to be collected and analyzed for Group 1: MenACYW Conjugate vaccine and Group 2: MENVEO® vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Anti-Pertussis toxoid (PT) | 37.5 ELISA units (EU)/mL |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Filamentous hemagglutinin (FHA) | 180 ELISA units (EU)/mL |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Pertactin (PRN) | 200 ELISA units (EU)/mL |
| Group 1: MenACYW Conjugate Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Fimbriae types 2 and 3 (FIM) | 339 ELISA units (EU)/mL |
| Group 2: MENVEO® Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Fimbriae types 2 and 3 (FIM) | 499 ELISA units (EU)/mL |
| Group 2: MENVEO® Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Anti-Pertussis toxoid (PT) | 44.4 ELISA units (EU)/mL |
| Group 2: MENVEO® Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Pertactin (PRN) | 265 ELISA units (EU)/mL |
| Group 2: MENVEO® Vaccine | Geometric Mean Concentrations (GMCs) of PT, FHA, PRN, and FIM Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Filamentous hemagglutinin (FHA) | 242 ELISA units (EU)/mL |
Comparison: PT: Geometric Mean Ratio95% CI: [0.722, 0.99]
Comparison: FHA: Geometric Mean Ratio95% CI: [0.661, 0.842]
Comparison: PRN: Geometric Mean Ratio95% CI: [0.627, 0.903]
Comparison: FIM: Geometric Mean Ratio95% CI: [0.525, 0.878]
Secondary
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3
A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.
Time frame: Within 7 days after vaccines injections at Day 0
Population: Analysis was performed on SafAS. Here Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | MenACYW site: Pain | 183 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | MenACYW site: Erythema | 15 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | MenACYW site: Swelling | 17 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | Tdap site: Pain | 286 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | Tdap site: Erythema | 28 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | Tdap site: Swelling | 24 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | HPV site: Pain | 288 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | HPV site: Erythema | 31 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines at Day 0: Group 3 | HPV site: Swelling | 26 Participants |
Secondary
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2
A Solicited Reaction (SR) was an Adverse Event (AE) that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.
Time frame: Within 7 days after vaccines injections at Day 0
Population: Analysis was performed on Safety Analysis Set (SafAS) defined as participants who received at least one dose of the study vaccine(s) and had any safety data available. All participants had their safety data analyzed according to vaccine(s) they actually received. Here, 'Number analyzed'=participants with available data for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Pain | 224 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Erythema | 25 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Swelling | 27 Participants |
| Group 2: MENVEO® Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Pain | 209 Participants |
| Group 2: MENVEO® Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Erythema | 37 Participants |
| Group 2: MENVEO® Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With MenACYW Conjugate Vaccine or MENVEO® Vaccine at Day 0: Group 1 and Group 2 | Swelling | 32 Participants |
Secondary
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4
A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions included: Pain, Erythema, and Swelling.
Time frame: Within 7 days after vaccines injections at Day 0
Population: Analysis was performed on SafAS. Here Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | Tdap site: Pain | 211 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | Tdap site: Erythema | 14 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | Tdap site: Swelling | 20 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | HPV site: Pain | 201 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | HPV site: Erythema | 16 Participants |
| Group 1: MenACYW Conjugate Vaccine | Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Vaccination With Tdap and HPV Vaccines at Day 0: Group 4 | HPV site: Swelling | 23 Participants |
Secondary
Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines
Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus antibodies were measured by ELISA.
Time frame: Day 30 (post-vaccination on Day 0)
Population: Analysis was performed on PPAS-1. Here Number analyzed' signifies number of participants with available data for specified category. Data for this outcome measure was not planned to be collected and analyzed for Group 1: MenACYW Conjugate vaccine and Group 2: MENVEO® vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Diphtheria | 97.8 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Tetanus | 99.7 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Diphtheria | 98.9 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Anti-Tetanus and Anti-Diphtheria Concentrations >= 1.0 International Unit (IU)/mL Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | Tetanus | 99.6 percentage of participants |
Comparison: Serogroup Diphtheria95% CI: [-3.3, 1.3]
Comparison: Serogroup Tetanus95% CI: [-1.2, 1.9]
Secondary
Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines
Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers \>= 1:8 for participants with pre-vaccination hSBA titers \< 1:8 or at least a 4-fold increase in hSBA titers from pre- to post vaccination for participants with pre-vaccination hSBA titers \>= 1:8.
Time frame: Day 30 (post-vaccination on Day 0)
Population: Analysis was performed on PPAS-1. Here 'Number analyzed' signifies number of participants with available data for specified category. Data for this outcome measure was not planned to be collected and analyzed for Group 4: Tdap+HPV.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup A | 75.6 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup C | 97.2 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup Y | 97.0 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup W | 86.2 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup W | 83.9 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup A | 80.6 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup Y | 95.6 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving hSBA Vaccine Seroresponse Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines | Serogroup C | 97.2 percentage of participants |
Comparison: Serogroup A95% CI: [-0.8, 10.5]
Comparison: Serogroup C95% CI: [-2.5, 2.4]
Comparison: Serogroup Y95% CI: [-4.3, 1.2]
Comparison: Serogroup W95% CI: [-7.3, 2.6]
Secondary
Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines
Anti-HPV 6, 11, 16, and 18 antibodies were measured using a competitive Luminex immunoassay. Seroconversion was defined as changing serostatus from seronegative to seropositive. Cutoff values for HPV seropositivity were \>= 20 milli-Merck units per milliliter (mMU/mL) for types 6 and 16, \>= 16 mMU/mL for type 11, and \>= 24mMU/mL for type 18.
Time frame: Day 210 (post-vaccination on Day 0)
Population: Per-Protocol Analysis Set-2(PPAS-2)defined for accessing HPV immune response data for participants in Group 3 \& 4 after they received third HPV vaccination at Visit 4(Day 180)\& completed blood sample at Visit 5(BL3 \[Day 210\]).Data for this outcome measure was not planned to be collected and analyzed for Groups 1 and 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 6 | 97.5 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 11 | 99.6 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 16 | 99.2 percentage of participants |
| Group 1: MenACYW Conjugate Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 18 | 99.2 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 18 | 98.8 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 6 | 95.7 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 16 | 98.8 percentage of participants |
| Group 2: MENVEO® Vaccine | Percentage of Participants Achieving Seroconversion for Anti-HPV6, HPV11, HPV16, and HPV18 Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine Given With Tdap and HPV Vaccines or Tdap and HPV Vaccines | HPV Type 11 | 98.8 percentage of participants |
Comparison: HPV Type 695% CI: [-1.8, 6.3]
Comparison: HPV Type 1195% CI: [-1.3, 3.9]
Comparison: HPV Type 1695% CI: [-1.9, 3.6]
Comparison: HPV Type 1895% CI: [-1.9, 3.6]