Dengue Fever
Conditions
Keywords
Drug therapy
Brief summary
The purpose of the study is to demonstrate the non-inferiority (NI) of the immune response to 2 doses of 9vHPV vaccine, 1 co-administered with TDV, compared with 2 doses of 9vHPV vaccine administered alone.
Detailed description
The vaccine being tested in this study is called Tetravalent Dengue Vaccine (TDV). The study will assess the immunogenicity and safety on the co-administration of 9vHPV vaccine with TDV in healthy participants aged ≥9 to \<15 years. The study will enroll approximately 614 healthy volunteers. Participants will be randomly assigned to one of the two treatment groups- * Group 1 * Group 2 All participants will receive recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) intramuscular (IM) in combination with Dengue Tetravalent Vaccine (TDV) subcutaneous (SC) injection on Day 1 (Month 0 ) followed by 9vHPV on Day 90 (Month 3) and TDV on Day 180 (Month 6) in Group 1. Participants will receive 9vHPV on Day 1 (Month 0) and Day 180 (Month 6) IM in Group 2. This multi-center trial will be conducted in Thailand. The overall time to participate in this study is 12 months. Participants will make multiple visits to the clinic, after last dose of study drug for a follow-up assessment.
Interventions
BIOLOGICAL9vHPV Vaccine
9vHPV intramuscular injection
BIOLOGICALDengue Tetravalent Vaccine (TDV)
TDV subcutaneous injection
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 14 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and the clinical judgment of the investigator. 2. Participants who can comply with trial procedures and are available for the duration of follow-up.
Exclusion criteria
1. Has an elevated oral temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccination. 2. Participants with contraindications, warnings and/or precautions to vaccination with Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) vaccine as specified within the prescribing information. 3. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease. 4. Known or suspected impairment/alteration of immune function, including: 1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed). 2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0). 3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial. 4. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0). 5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0). 6. Human immunodeficiency virus (HIV) infection or HIV-related disease. 7. Hepatitis B virus infection. 8. Hepatitis C virus infection. 9. Genetic immunodeficiency. 5. Abnormalities of splenic or thymic function. 6. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 7. Who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of trial vaccine administration. 8. Who have used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis versus treatment) must be documented. Trial entry should be delayed to allow for a full 24 hours to have passed since last use of antipyretics and/or analgesic medications. 9. Previous and planned vaccination (during the trial conduct), against any flavivirus (except Japanese encephalitis \[JE\]) including dengue, yellow fever (YF) viruses or tick-borne encephalitis. 10. Previous and planned vaccination (during the trial conduct) against HPV. 11. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile \[WN\] virus) candidate vaccine, except for participants who received placebo in those trials. 12. Has a current or previous infection with a flavivirus such as Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | Day 210 (Month 7) | GMTs for HPV were measured by immunoglobulin G binding assay (IgGBA) assay. HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58 were the types of HPV analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes | Day 120 (Month 4) | GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% (MNT50). The four dengue serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only. |
| Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes | Day 120 (Month 4) | Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only. Percentages are rounded off to the nearest decimal point. |
| Percentage of Participants With Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes | Day 120 (Month 4) | Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositive for multiple dengue serotypes were summarized for categories with at least one participant with event: trivalent (seropositive for 3 dengue serotypes), and tetravalent (seropositive for all 4 dengue serotypes). As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only. Percentages are rounded off to the nearest decimal point. |
| Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | Day 210 (Month 7) | Seropositive for HPV is defined as anti-HPV titers greater or equal to the prespecified cutoffs for any of the 9 HPV serotypes: HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58, measured by IgGBA. The serostatus cut-off is the antibody titer level above the assay's lower limit of quantification that reliably distinguishes sera samples classified by clinical likelihood of HPV infection and positive or negative status by previous versions of IgGBA or equivalent assay. The serostatus cut-offs for the 9 HPV serotypes: HPV-6= 9, HPV-11= 6, HPV-16= 5, HPV-18= 5, HPV-31= 3, HPV-33= 4, HPV-45= 3, HPV-52= 5 and HPV-58= 5. Percentages are rounded off to the nearest decimal point. |
| Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination | Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and included fever, headache, asthenia, malaise, and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4 degrees Fahrenheit \[°F\]). Only categories with at least one participant with event following any vaccination are reported. Percentages are rounded off to the nearest decimal point. The data for solicited systemic adverse events after any vaccination are presented. |
| Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination | Up to 28 days (Day of vaccination + 27 subsequent days) after each vaccination | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration. Percentages are rounded off to the nearest decimal point. The data for unsolicited adverse events after any vaccination are presented. |
| Percentage of Participants With Serious Adverse Events (SAEs) | From first vaccination (Day 1 [Month 0]) through end of study (Day 360 [Month 12]) | An SAE is defined as any untoward medical occurrence or effect that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important which may require intervention to prevent the items listed above or may expose the participant to danger. |
| Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Up to 7 days (Day of vaccination + 6 subsequent days) after each vaccination | Solicited local adverse events (AEs) (at injection site) were collected by participants using diary cards within 7 days after vaccination and included: Pain \[Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)\]; erythema and swelling \[Grade 0 (\<25 millimeters \[mm\]), 1 (25 - ≤ 50 mm), 2 (\>50 - ≤ 100 mm), 3 (\> 100 mm)\]. Percentages are rounded off to the nearest decimal point. The data for solicited local adverse events after any vaccination are presented. Only those categories with at least 1 participant with event are reported. |
Countries
Thailand
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Thailand from 15 May 2021 to 19 July 2022.
Pre-assignment details
Healthy participants aged ≥9 to \<15 years in endemic areas for dengue were enrolled in this study to receive recombinant 9-valent human papillomavirus vaccine (9vHPV) alone or with tetravalent dengue vaccine (TDV).
Participants by arm
| Arm | Count |
|---|---|
| 9vHPV+TDV Participants received 0.5 mL 9vHPV IM and 0.5 mL TDV SC once on Day 1 (Month 0) followed by 0.5 mL TDV SC once on Day 90 (Month 3) and 0.5 mL 9vHPV IM once on Day 180 (Month 6). | 307 |
| 9vHPV Participants received 0.5 mL 9vHPV IM once on Day 1 (Month 0) followed by 0.5 mL 9vHPV IM once on Day 180 (Month 6). | 307 |
| Total | 614 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Invalid Informed Consent Form (ICF) | 1 | 0 |
| Overall Study | Met Exclusion Criteria | 1 | 0 |
| Overall Study | Withdrawal of Consent | 3 | 3 |
Baseline characteristics
| Characteristic | 9vHPV+TDV | Total | 9vHPV |
|---|---|---|---|
| Age, Continuous | 11.1 years STANDARD_DEVIATION 1.6 | 11.2 years STANDARD_DEVIATION 1.59 | 11.3 years STANDARD_DEVIATION 1.59 |
| Body Mass Index (BMI) | 19.78 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 4.912 | 19.83 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 4.834 | 19.88 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 4.762 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 307 Participants | 614 Participants | 307 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 147.68 centimeters (cm) STANDARD_DEVIATION 12.244 | 147.93 centimeters (cm) STANDARD_DEVIATION 11.809 | 148.18 centimeters (cm) STANDARD_DEVIATION 11.374 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 307 Participants | 614 Participants | 307 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Thailand | 307 Participants | 614 Participants | 307 Participants |
| Sex: Female, Male Female | 150 Participants | 306 Participants | 156 Participants |
| Sex: Female, Male Male | 157 Participants | 308 Participants | 151 Participants |
| Weight | 44.21 kilograms (kg) STANDARD_DEVIATION 15.913 | 44.29 kilograms (kg) STANDARD_DEVIATION 15.101 | 44.37 kilograms (kg) STANDARD_DEVIATION 14.271 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 307 | 0 / 307 |
| other Total, other adverse events | 253 / 307 | 223 / 307 |
| serious Total, serious adverse events | 31 / 307 | 22 / 307 |
Outcome results
Primary
Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58
GMTs for HPV were measured by immunoglobulin G binding assay (IgGBA) assay. HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58 were the types of HPV analyzed.
Time frame: Day 210 (Month 7)
Population: The Per-protocol Set (PPS) excluded all participants seropositive to any HPV type at Baseline and included all participants from the Full Analysis Set (FAS) who had no major protocol violations. Overall number of participants analyzed is the number of participants available for analyses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-11 | 1342.745 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-33 | 1138.716 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-18 | 2309.629 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-45 | 504.033 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-16 | 7777.694 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-52 | 585.606 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-31 | 1690.941 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-58 | 1163.600 titer |
| 9vHPV+TDV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-6 | 1633.693 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-58 | 1284.504 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-6 | 1790.986 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-11 | 1325.192 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-16 | 7822.564 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-18 | 2506.309 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-31 | 1736.943 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-33 | 1179.469 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-45 | 584.198 titer |
| 9vHPV | Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 | HPV-52 | 561.007 titer |
Secondary
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes
GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% (MNT50). The four dengue serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only.
Time frame: Day 120 (Month 4)
Population: The PPS excluded all participants seropositive to any HPV type at Baseline and included all participants from the FAS who had no major protocol violations. Overall number of participants analyzed is the number of participants available for analyses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 9vHPV+TDV | GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes | DENV-1 | 719.1 titer |
| 9vHPV+TDV | GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes | DENV-2 | 1691.4 titer |
| 9vHPV+TDV | GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes | DENV-3 | 555.4 titer |
| 9vHPV+TDV | GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes | DENV-4 | 494.3 titer |
Secondary
Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration. Percentages are rounded off to the nearest decimal point. The data for unsolicited adverse events after any vaccination are presented.
Time frame: Up to 28 days (Day of vaccination + 27 subsequent days) after each vaccination
Population: Safety Set included all randomized participants who received at least 1 dose of IPs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination | 8.8 percentage of participants |
| 9vHPV | Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination | 2.6 percentage of participants |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence or effect that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important which may require intervention to prevent the items listed above or may expose the participant to danger.
Time frame: From first vaccination (Day 1 [Month 0]) through end of study (Day 360 [Month 12])
Population: Safety Set included all randomized participants who received at least 1 dose of IPs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Serious Adverse Events (SAEs) | 10.1 percentage of participants |
| 9vHPV | Percentage of Participants With Serious Adverse Events (SAEs) | 7.2 percentage of participants |
Secondary
Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes
Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only. Percentages are rounded off to the nearest decimal point.
Time frame: Day 120 (Month 4)
Population: The PPS excluded all participants seropositive to any HPV type at Baseline and included all participants from the FAS who had no major protocol violations. Overall number of participants analyzed is the number of participants available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes | DENV-4 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes | DENV-1 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes | DENV-2 | 99.6 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes | DENV-3 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA)
Seropositive for HPV is defined as anti-HPV titers greater or equal to the prespecified cutoffs for any of the 9 HPV serotypes: HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58, measured by IgGBA. The serostatus cut-off is the antibody titer level above the assay's lower limit of quantification that reliably distinguishes sera samples classified by clinical likelihood of HPV infection and positive or negative status by previous versions of IgGBA or equivalent assay. The serostatus cut-offs for the 9 HPV serotypes: HPV-6= 9, HPV-11= 6, HPV-16= 5, HPV-18= 5, HPV-31= 3, HPV-33= 4, HPV-45= 3, HPV-52= 5 and HPV-58= 5. Percentages are rounded off to the nearest decimal point.
Time frame: Day 210 (Month 7)
Population: The PPS excluded all participants seropositive to any HPV type at Baseline and included all participants from the FAS who had no major protocol violations. Overall number of participants analyzed is the number of participants available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-11 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-33 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-18 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-45 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-16 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-52 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-31 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-58 | 100.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-6 | 100.0 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-58 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-6 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-11 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-16 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-18 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-31 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-33 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-45 | 99.1 percentage of participants |
| 9vHPV | Percentage of Participants With Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) | HPV-52 | 99.1 percentage of participants |
Secondary
Percentage of Participants With Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes
Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositive for multiple dengue serotypes were summarized for categories with at least one participant with event: trivalent (seropositive for 3 dengue serotypes), and tetravalent (seropositive for all 4 dengue serotypes). As prespecified in the protocol, the data for this outcome measure was collected and analyzed for participants in the 9vHPV+TDV arm group only. Percentages are rounded off to the nearest decimal point.
Time frame: Day 120 (Month 4)
Population: The PPS excluded all participants seropositive to any HPV type at Baseline and included all participants from the FAS who had no major protocol violations. Overall number of participants analyzed is the number of participants available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes | Trivalent | 0.4 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes | Tetravalent | 99.6 percentage of participants |
Secondary
Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity
Solicited local adverse events (AEs) (at injection site) were collected by participants using diary cards within 7 days after vaccination and included: Pain \[Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)\]; erythema and swelling \[Grade 0 (\<25 millimeters \[mm\]), 1 (25 - ≤ 50 mm), 2 (\>50 - ≤ 100 mm), 3 (\> 100 mm)\]. Percentages are rounded off to the nearest decimal point. The data for solicited local adverse events after any vaccination are presented. Only those categories with at least 1 participant with event are reported.
Time frame: Up to 7 days (Day of vaccination + 6 subsequent days) after each vaccination
Population: Safety Set included all randomized participants who received at least 1 dose of IPs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Mild | 54.1 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Moderate | 9.5 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Severe | 0.7 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Erythema: Mild | 7.5 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Erythema: Moderate | 0.7 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Swelling: Mild | 3.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Erythema: Moderate | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Mild | 42.8 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Erythema: Mild | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Moderate | 6.5 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Swelling: Mild | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity | Pain: Severe | 0 percentage of participants |
Secondary
Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity
Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and included fever, headache, asthenia, malaise, and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4 degrees Fahrenheit \[°F\]). Only categories with at least one participant with event following any vaccination are reported. Percentages are rounded off to the nearest decimal point. The data for solicited systemic adverse events after any vaccination are presented.
Time frame: Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination
Population: Safety Set included all randomized participants who received at least 1 dose of IPs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Moderate | 2.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Severe | 0.3 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Moderate | 3.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Mild | 36.1 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Severe | 0.3 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Moderate | 7.9 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Mild | 16.7 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Severe | 0.3 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Mild | 17.7 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 38.0°C to <38.5°C | 2.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Mild | 20.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 38.5°C to <39.0°C | 0.3 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Moderate | 2.0 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 39.0°C to <39.5°C | 0.3 percentage of participants |
| 9vHPV+TDV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Severe | 0.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 39.0°C to <39.5°C | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Mild | 18.0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Moderate | 0.7 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Headache: Severe | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Mild | 12.1 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Moderate | 1.0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Asthenia: Severe | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Mild | 10.5 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Moderate | 1.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Malaise: Severe | 0 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Mild | 27.8 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Moderate | 2.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Myalgia: Severe | 0.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 38.0°C to <38.5°C | 0.3 percentage of participants |
| 9vHPV | Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity | Fever: 38.5°C to <39.0°C | 0 percentage of participants |