Meningococcal Meningitis
Conditions
Keywords
meningitis, human papillomavirus, tetanus, diptheria, pertussis
Brief summary
The main objective is to determine whether immune responses to Tdap (GlaxoSmithKline, Boostrix®) and HPV vaccine (Merck & Co., Inc., Gardasil®) when administered concomitantly with MenACWY are comparable to responses elicited by these vaccines when given alone.
Interventions
BIOLOGICALPlacebo + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
All three vaccines were administered concomitantly. Quadrivalent Human Papillomavirus \[Types 6, 11, 16, 18\] Recombinant Vaccine is GARDASIL®. Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine(Tdap) is Boostrix®.
BIOLOGICALMenACWY-CRM Conjugate Vaccine + Combined Tetanus, Reduced Diphtheria Toxoid, Acellular Pertussis Vaccine + Quadrivalent Human Papillomavirus Vaccine
All three vaccines were administered concomitantly. MenACWY-CRM contains diphtheria-like toxoid as carrier for the capsular polysaccharides. Quadrivalent Human Papillomavirus \[Types 6, 11, 16, 18\] Recombinant Vaccine is GARDASIL®. Reduced Diphtheria Toxoid,Acellular Pertussis Vaccine(Tdap) is Boostrix®.
Sponsors
Novartis Vaccines
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
11 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
Individuals eligible for enrollment in this study were female and male individuals who had been shown to be healthy and who were: 1. 11-18 years of age inclusive who had given their written consent/assent and if applicable, whose parents or legal guardians had given written informed consent at the time of enrollment; * Available for all visits and telephone calls scheduled for the study; * In good health as determined by: * Medical history * Physical assessment * Clinical judgment of the investigator 2. Had been properly vaccinated against diphtheria, tetanus, and pertussis per local regulations; 3. Subjects who were current with childhood DTP-containing vaccinations per local guidelines. Any previous vaccinations containing DTP must have been received at least 5 years before study enrollment and no prior adolescent vaccinations (11-18 years of age) containing DTP vaccines were allowed. 4. For female subjects, who had a negative urine pregnancy test. 5. Any female subject who is sexually active committed to practice appropriate birth control.
Exclusion criteria
Individuals not eligible to be enrolled in the study were those: 1. Who were unwilling to give their written assent / consent 2. Who were breastfeeding 3. Who was, and/or whose parents or legal guardians were perceived to be unreliable or unavailable for the duration of the study period 4. Who had previous confirmed or suspected disease caused by N. meningitidis 5. Who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment 6. Who had previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational). (Exception: Receipt of OMP-containing Hib vaccines was permitted) 7. Who had received prior human papillomavirus (HPV) vaccine 8. Who had received investigational agents or vaccines within 30 days prior to enrollment or who expected to receive an investigational agent or vaccine prior to completion of the study 9. Who had received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine is anticipated during the study period. (Exception: Influenza vaccine could be administered up to 15 days prior to each study immunization and no less than 15 days after each study vaccination) 10. Who had experienced, within the 7 days prior to enrollment, significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment 11. Who had any serious acute, chronic or progressive disease such as * History of cancer * Complicated diabetes mellitus * Advanced arteriosclerotic disease * Autoimmune disease * HIV infection or AIDS * Blood dyscrasias * Congestive heart failure * Renal failure * Severe malnutrition (Note: Subjects with mild asthma were eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids were not eligible for enrollment) 12. Who had epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome 13. Who had a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including latex allergy 14. Who had a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example): * Receipt of immunosuppressive therapy within 30 days prior to enrollment (systemic corticosteroids administered for more than 5 days, or in a daily dose \> 1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy) * Receipt of immunostimulants * Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study 15. Who were known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; 16. Who have Down's syndrome or other known cytogenic disorders; 17. Who and/or whose families were planning to leave the area of the study site before the end of the study period; 18. Who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives. 19. Who were relatives of the study personnel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | 1 month post Tdap vaccination. | The percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL (as measured by ELISA) following concomitant administration of Tdap with HPV and MenACWY-CRM vaccine as compared to concomitant administration of Tdap with HPV and placebo. |
| Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | 1 month post Tdap vaccination. | The geometric mean concentrations (GMCs) of antibodies against pertussis antigens (PT, FHA and PRN), as measured by ELISA, following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | 1 month post MenACWY-CRM vaccination. | The immunogenicity was assessed in terms of geometric mean hSBA titers of MenACWY when administered concomitantly with Tdap and HPV at 1 month after 1 dose of MenACWY vaccination. |
| Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Day 1-7 after any vaccination. | The number of subjects reporting solicited local and systemic reactions following concomitant administration of MenACWY-CRM vaccine, Tdap and HPV vaccine as compared to concomitant administration of placebo with Tdap and HPV. |
| Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Throughout the study (Day 1 to Day 211). | The number of subjects reporting any unsolicited adverse reactions (AEs) when Tdap and HPV are concomitantly administered with MenACWY-CRM as compared to when Tdap and HPV vaccine are concomitantly administered with placebo. Note: A total of 2 MenACWY-CRM+Tdap+HPV subjects reported AEs leading to premature withdrawal - one subject due to treatment emergent AE and another subject prior to study vaccination on day 1. |
Countries
Italy, United States
Participant flow
Recruitment details
Subjects were enrolled in two countries (US and Italy).
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| MenACWY-CRM+Tdap+HPV Subjects received one dose of Tdap, MenACWY-CRM, and HPV concomitantly on day 1. A second and third dose of HPV was administered at 2 and 6 months, respectively, after the first dose. | 402 |
| Placebo+Tdap+HPV Subjects received one dose of Tdap, placebo, and HPV concomitantly on day 1. A second and third dose of HPV was administered at 2 and 6 months, respectively, after the first dose. | 399 |
| Total | 801 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reason | 1 | 0 |
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 16 | 12 |
| Overall Study | Protocol Violation | 4 | 3 |
| Overall Study | Unable to Classify | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 12 |
Baseline characteristics
| Characteristic | MenACWY-CRM+Tdap+HPV | Placebo+Tdap+HPV | Total |
|---|---|---|---|
| Age, Continuous | 11.9 years STANDARD_DEVIATION 1.7 | 11.8 years STANDARD_DEVIATION 1.5 | 11.9 years STANDARD_DEVIATION 1.6 |
| Sex: Female, Male Female | 169 Participants | 155 Participants | 324 Participants |
| Sex: Female, Male Male | 233 Participants | 244 Participants | 477 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 288 / 396 | 248 / 397 |
| serious Total, serious adverse events | 4 / 396 | 3 / 397 |
Outcome results
Primary
Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo
The geometric mean concentrations (GMCs) of antibodies against pertussis antigens (PT, FHA and PRN), as measured by ELISA, following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.
Time frame: 1 month post Tdap vaccination.
Population: Analysis was done on the Tdap per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PT (Day 1) (N= 375, 380) | 4.77 EU/mL |
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PT(One month post dose) | 44 EU/mL |
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | FHA (Day 1) (N= 375, 380) | 24 EU/mL |
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | FHA (One month post dose) | 202 EU/mL |
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PRN (Day 1) (N= 375, 380) | 20 EU/mL |
| MenACWY-CRM+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PRN (One month post dose) | 330 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PRN (Day 1) (N= 375, 380) | 21 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PT (Day 1) (N= 375, 380) | 4.16 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | FHA (One month post dose) | 240 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PT(One month post dose) | 44 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | PRN (One month post dose) | 403 EU/mL |
| Placebo+Tdap+HPV | Geometric Mean Concentrations of Antibodies Against Pertussis Antigens After Concomitant Administration of Tdap With HPV and MenACWY-CRM Compared to Concomitant Administration of Tdap With HPV and Placebo | FHA (Day 1) (N= 375, 380) | 21 EU/mL |
Comparison: Non-inferiority of anti-PT immune response following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.95% CI: [0.89, 1.14]ANOVA
Comparison: Non-inferiority of anti-FHA immune response following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.95% CI: [0.76, 0.93]ANOVA
Comparison: Non-inferiority of anti-PRN immune response following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.95% CI: [0.72, 0.93]ANOVA
Primary
Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo
The percentages of subjects with anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL (as measured by ELISA) following concomitant administration of Tdap with HPV and MenACWY-CRM vaccine as compared to concomitant administration of Tdap with HPV and placebo.
Time frame: 1 month post Tdap vaccination.
Population: Analysis was done on the Tdap per-protocol population, i.e., all subjects who received all the relevant doses of vaccine correctly, and provided serology results at one month postvaccination, and had no major protocol violation as defined prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | Day 1 (diphtheria) (N=375, 380) | 5 percentages of subjects |
| MenACWY-CRM+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | One month post dose (diphtheria) | 95 percentages of subjects |
| MenACWY-CRM+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | Day 1 (tetanus ) (N=375, 380) | 28 percentages of subjects |
| MenACWY-CRM+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | One month post dose (tetanus ) | 99 percentages of subjects |
| Placebo+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | One month post dose (tetanus ) | 98 percentages of subjects |
| Placebo+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | Day 1 (diphtheria) (N=375, 380) | 3 percentages of subjects |
| Placebo+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | Day 1 (tetanus ) (N=375, 380) | 28 percentages of subjects |
| Placebo+Tdap+HPV | Percentages of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentrations ≥ 0.1 IU/mL When Tdap is Administered Concomitantly With HPV and MenACWY-CRM Vaccine Compared to Tdap Given Concomitantly With HPV and Placebo | One month post dose (diphtheria) | 82 percentages of subjects |
Comparison: Non-inferiority of anti-diphtheria immune response following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo95% CI: [9, 17]Miettinen and Nurminen
Comparison: Non-inferiority of anti-tetanus immune response following concomitant administration of Tdap with HPV and MenACWY-CRM as compared to concomitant administration of Tdap with HPV and placebo.95% CI: [-2, 2]Miettinen and Nurminen
Secondary
Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination.
The immunogenicity was assessed in terms of geometric mean hSBA titers of MenACWY when administered concomitantly with Tdap and HPV at 1 month after 1 dose of MenACWY vaccination.
Time frame: 1 month post MenACWY-CRM vaccination.
Population: Analysis was done on the MenACWY per-protocol population - all subjects who received all the relevant doses of vaccine correctly, and provided evaluable serum samples at baseline and one month postvaccination for at least one serogroup, and had no major protocol violation as defined prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men A | 35 Titers |
| MenACWY-CRM+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men C (N=370, 97) | 59 Titers |
| MenACWY-CRM+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men Y (N=369, 97) | 48 Titers |
| MenACWY-CRM+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men W (N=369, 96) | 61 Titers |
| Placebo+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men Y (N=369, 97) | 3.54 Titers |
| Placebo+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men A | 2.13 Titers |
| Placebo+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men C (N=370, 97) | 3.92 Titers |
| Placebo+Tdap+HPV | Geometric Mean hSBA Titers Against N. Meningitidis Serogroups A,C,W and Y at 1 Month After Men ACWY Vaccination. | Men W (N=369, 96) | 12 Titers |
Secondary
Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo
The number of subjects reporting solicited local and systemic reactions following concomitant administration of MenACWY-CRM vaccine, Tdap and HPV vaccine as compared to concomitant administration of placebo with Tdap and HPV.
Time frame: Day 1-7 after any vaccination.
Population: Analysis was done on solicited safety Set - All subjects in the exposed population who provided solicited AEs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Local | 209 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site pain | 158 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site erythema | 65 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site induration | 61 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Systemic | 205 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Chills | 60 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Nausea | 54 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Malaise | 57 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Myalgia | 115 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Arthralgia | 35 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Headache | 113 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Rash | 4 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Fever ≥ 38°C | 9 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Other | 88 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Stayed home due to reaction | 25 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Analgesic / Antipyretic medication used | 74 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Analgesic / Antipyretic medication used | 65 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Local | 164 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Myalgia | 101 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site pain | 134 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Fever ≥ 38°C | 8 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site erythema | 25 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Arthralgia | 43 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Injection site induration | 37 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Stayed home due to reaction | 33 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Systemic | 179 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Headache | 95 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Chills | 50 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Other | 80 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Nausea | 39 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Rash | 7 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Solicited Local and Systemic Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Malaise | 44 Subjects |
Secondary
Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo
The number of subjects reporting any unsolicited adverse reactions (AEs) when Tdap and HPV are concomitantly administered with MenACWY-CRM as compared to when Tdap and HPV vaccine are concomitantly administered with placebo. Note: A total of 2 MenACWY-CRM+Tdap+HPV subjects reported AEs leading to premature withdrawal - one subject due to treatment emergent AE and another subject prior to study vaccination on day 1.
Time frame: Throughout the study (Day 1 to Day 211).
Population: Analysis was done on overall safety population - All subjects in the exposed population who provided postvaccination and post-baseline safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Any AEs | 201 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | At least possibly related AEs | 17 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Serious AEs | 4 Subjects |
| MenACWY-CRM+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | AEs leading to Premature Withdrawal | 2 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | AEs leading to Premature Withdrawal | 0 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Any AEs | 197 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | Serious AEs | 3 Subjects |
| Placebo+Tdap+HPV | Number of Subjects With Unsolicited Adverse Events When Tdap and HPV Are Concomitantly Administered With MenACWY-CRM Compared to When Tdap and HPV Are Concomitantly Administered With Placebo | At least possibly related AEs | 14 Subjects |