Diphtheria, Neoplasms, Glandular and Epithelial, Poliomyelitis, Tetanus, Whooping Cough
Conditions
Brief summary
Data from this study are expected to demonstrate that Gardasil (V501, Human Papillomavirus \[Types 6, 11, 16, 18\] Recombinant Vaccine), when administered concomitantly with a combined diphtheria, tetanus, pertussis, and poliomyelitis vaccine in adolescents remains immunogenic and well-tolerated and it does not impair the immunogenicity of the concomitant vaccines.
Interventions
BIOLOGICALComparator: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant (qHPV) Vaccine from Current Manufacturing Facility (CMF)
GARDASIL™ (quadrivalent human papillomavirus \[types 6, 11, 16, 18\] virus-like particle \[VLP\] vaccine, referred to as qHPV vaccine) made at the current manufacturing facility was administered as 0.5-mL intramuscular dose at Day 1, Month 2, and Month 6.
BIOLOGICALComparator: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant (qHPV) Vaccine from Future Manufacturing Facility (FMF)
GARDASIL™ (quadrivalent human papillomavirus \[types 6, 11, 16, 18\] virus-like particle \[VLP\] vaccine, referred to as qHPV vaccine) made at the future manufacturing facility was administered as 0.5-mL intramuscular dose at Day 1, Month 2, and Month 6.
BIOLOGICALComparator: REPEVAX™ (Concomitant)
REPEVAX™ (diphtheria, tetanus, pertussis \[acellular, component\] and poliomyelitis \[inactivated\] vaccine, Sanofi Pasteur, Swiftwater, PA U.S.A) was administered as a single 0.5-mL intramuscular dose at Day 1 in a limb opposite that of quadrivalent HPV injection.
BIOLOGICALComparator: REPEVAX™ (Non-Concomitant)
REPEVAX™ (diphtheria, tetanus, pertussis \[acellular, component\] and poliomyelitis \[inactivated\] vaccine, Sanofi Pasteur, Swiftwater, PA U.S.A) was administered as a single 0.5-mL intramuscular dose at Month 1 in a limb opposite that of quadrivalent HPV injection.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be healthy boys or girls, 11-17 years of age * Must be a virgin with no intention of becoming sexually active during the study period * Must have been properly vaccinated against diphtheria, tetanus, pertussis and polio
Exclusion criteria
* Must not have received a vaccine against diphtheria, tetanus, pertussis and polio in the past 5 years * Must not have received any prior human papillomavirus (HPV) vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) for Anti-HPV 6 at Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Serum antibodies to HPV Type 6 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) for Anti-HPV 11 at Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Serum antibodies to HPV Type 11 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) for Anti-HPV 16 at Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Serum antibodies to HPV Type 16 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) for Anti-HPV 18 at Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Serum antibodies to HPV Type 18 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Number of Participants Who Seroconverted for HPV Type 6 (HPV 6 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Seroconversion to HPV Type 6 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥20 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Seroconverted for HPV Type 11 (HPV 11 ≥16 mMU/mL) by Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Seroconversion to HPV Type 11 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥16 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Seroconverted for HPV Type 16 (HPV 16 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Seroconversion to HPV Type 16 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥20 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Seroconverted for HPV Type 18 (HPV 18 ≥24 mMU/mL) by Month 7 (4 Weeks Postdose 3) | Up to 7 Months (4 Weeks Postdose 3) | Seroconversion to HPV Type 18 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥24 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Achieved Acceptable Levels of Titers to Diphtheria (Diphtheria ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Diphtheria antitoxin titers were measured using a neutralization assay in Vero cell culture that compares the antitoxin level in the serum of participants with the World Health Organization International Standard for Diphtheria Antitoxin. An acceptable level of response was defined as ≥0.1 International Units (IU)/milliliter (mL). Response levels of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Tetanus antitoxin titers were measured using an indirect, non-competitive enzyme immunoassay (EIA) that compares the antitoxin level in the serum of participants with the World Health Organization International Standard for Tetanus Immunoglobulin. An acceptable level of response was defined as ≥0.1 International Units (IU)/milliliter (mL). Response levels of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 1 (Poliovirus Type 1 ≥1:8) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 2 (Poliovirus Type 2 ≥1:8) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 3 (Poliovirus Type 3 ≥1:8) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine. |
| Geometric Mean Titers (GMTs) For Pertussis (Anti-PT) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Serum antibodies to Pertussis Toxoid Antibody (anti-PT) were measured with an enzyme-linked immunosorbent assay (ELISA). Titers were reported in ELISA units/mL (ELU/mL) and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) For Pertussis (Anti-FHA) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Serum antibodies to Pertussis Filamentous Haemagglutin Antibody (anti-FHA) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 3.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) For Pertussis (Anti-PRN) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Serum antibodies to Pertussis Pertactin (anti-PRN) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
| Geometric Mean Titers (GMTs) For Pertussis (Anti-FIM) One Month Postvaccination With REPEVAX™ | Up to 1 Month (1 Month Postdose 1) | Serum antibodies to Pertussis Fimbrial Agglutinogens Antibody (anti-FIM) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV Type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction. |
Participant flow
Pre-assignment details
The study enrolled healthy participants, 11-17 years old, with 0 lifetime sexual partners, vaccinated against diphtheria, tetanus, pertussis and polio but had not received the vaccine in the past 5 years or any prior human papillomavirus (HPV) vaccine. Additional inclusion and exclusion criteria applied.
Participants by arm
| Arm | Count |
|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant (qHPV) vaccine and REPEVAX™ administered on Day 1 at different injection sites. | 419 |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant (qHPV) vaccine administered on Day 1 followed by REPEVAX™ administered at Month 1. | 424 |
| Total | 843 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Anorexia | 1 | 0 |
| Overall Study | Lack of Time | 1 | 1 |
| Overall Study | Unwilling to Continue | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | qHPV Vaccine + REPEVAX™ (Concomitant) | qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Total |
|---|---|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 1.5 | 12.1 years STANDARD_DEVIATION 1.5 | 12.1 years STANDARD_DEVIATION 1.5 |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Black | 3 participants | 3 participants | 6 participants |
| Race/Ethnicity, Customized Multi-racial | 2 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized White | 413 participants | 415 participants | 828 participants |
| Sex: Female, Male Female | 295 Participants | 288 Participants | 583 Participants |
| Sex: Female, Male Male | 124 Participants | 136 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 405 / 420 | 406 / 423 |
| serious Total, serious adverse events | 1 / 420 | 3 / 423 |
Outcome results
Primary
Geometric Mean Titers (GMTs) for Anti-HPV 11 at Month 7 (4 Weeks Postdose 3)
Serum antibodies to HPV Type 11 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 11 at Month 7 (4 Weeks Postdose 3) | 1338.3 milliMerck units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 11 at Month 7 (4 Weeks Postdose 3) | 1460.7 milliMerck units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) for Anti-HPV 16 at Month 7 (4 Weeks Postdose 3)
Serum antibodies to HPV Type 16 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 16 at Month 7 (4 Weeks Postdose 3) | 5835.7 milliMerck units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 16 at Month 7 (4 Weeks Postdose 3) | 6508.1 milliMerck units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) for Anti-HPV 18 at Month 7 (4 Weeks Postdose 3)
Serum antibodies to HPV Type 18 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 18 at Month 7 (4 Weeks Postdose 3) | 1096.0 milliMerck units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 18 at Month 7 (4 Weeks Postdose 3) | 1308.8 milliMerck units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) for Anti-HPV 6 at Month 7 (4 Weeks Postdose 3)
Serum antibodies to HPV Type 6 were measured with a Competitive Luminex Immunoassay. Titers were reported in milli Merck Units (mMU)/milliliter (mL). GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 6 at Month 7 (4 Weeks Postdose 3) | 1151.3 milliMerck units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) for Anti-HPV 6 at Month 7 (4 Weeks Postdose 3) | 1244.9 milliMerck units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) For Pertussis (Anti-FHA) One Month Postvaccination With REPEVAX™
Serum antibodies to Pertussis Filamentous Haemagglutin Antibody (anti-FHA) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 3.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-FHA) One Month Postvaccination With REPEVAX™ | 140.3 ELISA units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-FHA) One Month Postvaccination With REPEVAX™ | 140.7 ELISA units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) For Pertussis (Anti-FIM) One Month Postvaccination With REPEVAX™
Serum antibodies to Pertussis Fimbrial Agglutinogens Antibody (anti-FIM) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs for each HPV Type using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-FIM) One Month Postvaccination With REPEVAX™ | 561.2 ELISA units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-FIM) One Month Postvaccination With REPEVAX™ | 506.4 ELISA units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) For Pertussis (Anti-PRN) One Month Postvaccination With REPEVAX™
Serum antibodies to Pertussis Pertactin (anti-PRN) were measured with an ELISA. Titers were reported in ELU/mL and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-PRN) One Month Postvaccination With REPEVAX™ | 504.1 ELISA units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-PRN) One Month Postvaccination With REPEVAX™ | 552.8 ELISA units/mL |
p-value: <0.001ANOVA
Primary
Geometric Mean Titers (GMTs) For Pertussis (Anti-PT) One Month Postvaccination With REPEVAX™
Serum antibodies to Pertussis Toxoid Antibody (anti-PT) were measured with an enzyme-linked immunosorbent assay (ELISA). Titers were reported in ELISA units/mL (ELU/mL) and the lower limit of quantitation for the assay was 5.0 ELU/mL. GMTs from participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to GMTs from participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared GMTs using an ANOVA model with a response of log individual titers and fixed effects for treatment group, manufacturing facility, study site, and the treatment-by-site interaction.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-PT) One Month Postvaccination With REPEVAX™ | 38.1 ELISA units/mL |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Geometric Mean Titers (GMTs) For Pertussis (Anti-PT) One Month Postvaccination With REPEVAX™ | 35.7 ELISA units/mL |
p-value: <0.001ANOVA
Primary
Number of Participants Who Achieved Acceptable Levels of Titers to Diphtheria (Diphtheria ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™
Diphtheria antitoxin titers were measured using a neutralization assay in Vero cell culture that compares the antitoxin level in the serum of participants with the World Health Organization International Standard for Diphtheria Antitoxin. An acceptable level of response was defined as ≥0.1 International Units (IU)/milliliter (mL). Response levels of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Diphtheria (Diphtheria ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | 380 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Diphtheria (Diphtheria ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | 379 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 1 (Poliovirus Type 1 ≥1:8) One Month Postvaccination With REPEVAX™
Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 1 (Poliovirus Type 1 ≥1:8) One Month Postvaccination With REPEVAX™ | 367 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 1 (Poliovirus Type 1 ≥1:8) One Month Postvaccination With REPEVAX™ | 376 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 2 (Poliovirus Type 2 ≥1:8) One Month Postvaccination With REPEVAX™
Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 2 (Poliovirus Type 2 ≥1:8) One Month Postvaccination With REPEVAX™ | 369 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 2 (Poliovirus Type 2 ≥1:8) One Month Postvaccination With REPEVAX™ | 376 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 3 (Poliovirus Type 3 ≥1:8) One Month Postvaccination With REPEVAX™
Poliovirus antibody was measured using a poliovirus neutralization assay that assesses the ability of serial dilutions of participant sera to neutralize known amounts of type-specific Sabin poliovirus strains (Types 1, 2, and 3). An acceptable level of response was defined as participants who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution of sera. The response of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 3 (Poliovirus Type 3 ≥1:8) One Month Postvaccination With REPEVAX™ | 360 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Poliovirus Type 3 (Poliovirus Type 3 ≥1:8) One Month Postvaccination With REPEVAX™ | 375 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™
Tetanus antitoxin titers were measured using an indirect, non-competitive enzyme immunoassay (EIA) that compares the antitoxin level in the serum of participants with the World Health Organization International Standard for Tetanus Immunoglobulin. An acceptable level of response was defined as ≥0.1 International Units (IU)/milliliter (mL). Response levels of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) were compared to participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared response levels using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 1 Month (1 Month Postdose 1)
Population: Per-protocol population: participants must have no major protocol violations and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | 381 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Achieved Acceptable Levels of Titers to Tetanus (Tetanus ≥0.1 IU/mL) One Month Post-vaccination With REPEVAX™ | 380 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Seroconverted for HPV Type 11 (HPV 11 ≥16 mMU/mL) by Month 7 (4 Weeks Postdose 3)
Seroconversion to HPV Type 11 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥16 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Seroconverted for HPV Type 11 (HPV 11 ≥16 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 367 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Seroconverted for HPV Type 11 (HPV 11 ≥16 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 376 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Seroconverted for HPV Type 16 (HPV 16 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3)
Seroconversion to HPV Type 16 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥20 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Seroconverted for HPV Type 16 (HPV 16 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 370 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Seroconverted for HPV Type 16 (HPV 16 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 378 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Seroconverted for HPV Type 18 (HPV 18 ≥24 mMU/mL) by Month 7 (4 Weeks Postdose 3)
Seroconversion to HPV Type 18 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥24 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Seroconverted for HPV Type 18 (HPV 18 ≥24 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 372 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Seroconverted for HPV Type 18 (HPV 18 ≥24 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 378 participants |
p-value: <0.001Miettinen and Nurminen
Primary
Number of Participants Who Seroconverted for HPV Type 6 (HPV 6 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3)
Seroconversion to HPV Type 6 was defined as changing serostatus from seronegative to seropositive as measured by GMT. The cutoff value for HPV seropositivity was ≥20 mMU/mL. Seroconversion of participants who received qHPV vaccine and REPEVAX™ together at Day 1 (concomitant) was compared to seroconversion of participants who received qHPV vaccine at Day 1 followed by REPEVAX™ 1 month later (non-concomitant). An analysis of non-inferiority compared seroconversion for each HPV type using methods developed by Miettinen and Nurminen adjusting for manufacturing facility for qHPV vaccine.
Time frame: Up to 7 Months (4 Weeks Postdose 3)
Population: Per-protocol population: participants must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| qHPV Vaccine + REPEVAX™ (Concomitant) | Number of Participants Who Seroconverted for HPV Type 6 (HPV 6 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 367 participants |
| qHPV Vaccine + REPEVAX™ (Non-Concomitant) | Number of Participants Who Seroconverted for HPV Type 6 (HPV 6 ≥20 mMU/mL) by Month 7 (4 Weeks Postdose 3) | 375 participants |
p-value: <0.001Miettinen and Nurminen