A Phase 3 interventional study of 9vHPV Vaccine and Dengue Tetravalent Vaccine (TDV) in Dengue Fever, sponsored by Takeda. Completed at 4 sites in Thailand. Open to participants aged 9 Years to 14 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-07.
Sponsored by Takeda · Phase 3, Interventional, and Prevention
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.
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-
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.
279 studies on the registry are indexed under Dengue; 45 are open to participants now.
This study's enrollment of 614 is above the median of 123 across 195 interventional studies indexed under Dengue.
Browse Dengue studies →Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.
Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Known or suspected impairment/alteration of immune function, including:
Participants will receive 0.5 mL 9vHPV intramuscularly (IM) with 0.5 mL TDV subcutaneously (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).
Biological: 9vHPV Vaccine · Biological: Dengue Tetravalent Vaccine (TDV)
Participants will receive 0.5 mL 9vHPV vaccine IM once on Day 1 (Month 0) followed by 0.5 mL 9vHPV vaccine IM once on Day 180 (Month 6).
Biological: 9vHPV Vaccine
9vHPV intramuscular injection
TDV subcutaneous injection
Also known as: TAK-003
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)
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)
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)
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)
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)
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
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
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
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])
Participants took part in the study at 4 investigative sites in Thailand from 15 May 2021 to 19 July 2022.
| Milestone | 9vHPV+TDV | 9vHPV |
|---|---|---|
| Started | 307 | 307 |
| Completed | 302 | 304 |
| Not completed | 5 | 3 |
| Withdrew: Withdrawal of consent | 3 | 3 |
| Withdrew: Met exclusion criteria | 1 | 0 |
| Withdrew: Invalid informed consent form (icf) | 1 | 0 |
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.
| titer | 9vHPV+TDV | 9vHPV |
|---|---|---|
| HPV-6 | 1633.693 (1465.31 to 1821.43) | 1790.986 (1556.08 to 2061.35) |
| HPV-11 | 1342.745 (1225.64 to 1471.04) | 1325.192 (1164.58 to 1507.95) |
| HPV-16 | 7777.694 (6989.76 to 8654.45) | 7822.564 (6701.83 to 9130.71) |
| HPV-18 | 2309.629 (2075.91 to 2569.66) | 2506.309 (2182.67 to 2877.93) |
| HPV-31 | 1690.941 (1529.39 to 1869.55) | 1736.943 (1515.05 to 1991.33) |
| HPV-33 | 1138.716 (1019.66 to 1271.67) | 1179.469 (1033.66 to 1345.84) |
| HPV-45 | 504.033 (453.46 to 560.24) | 584.198 (509.91 to 669.31) |
| HPV-52 | 585.606 (533.44 to 642.87) | 561.007 (492.77 to 638.69) |
| HPV-58 | 1163.600 (1060.23 to 1277.05) | 1284.504 (1130.63 to 1459.32) |
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 | 9vHPV+TDV | 9vHPV |
|---|---|---|
| HPV-6 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-11 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-16 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-18 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-31 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-33 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-45 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-52 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
| HPV-58 | 100.0 (98.5 to 100.0) | 99.1 (96.9 to 99.9) |
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.
| titer | 9vHPV+TDV |
|---|---|
| DENV-1 | 719.1 (577.8 to 895.0) |
| DENV-2 | 1691.4 (1411.0 to 2027.4) |
| DENV-3 | 555.4 (462.8 to 666.6) |
| DENV-4 | 494.3 (420.8 to 580.6) |
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 | 9vHPV+TDV |
|---|---|
| DENV-1 | 100.0 (98.5 to 100.0) |
| DENV-2 | 99.6 (97.7 to 100.0) |
| DENV-3 | 100.0 (98.5 to 100.0) |
| DENV-4 | 100.0 (98.5 to 100.0) |
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 | 9vHPV+TDV |
|---|---|
| Trivalent | 0.4 (0.0 to 2.3) |
| Tetravalent | 99.6 (97.7 to 100.0) |
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.
| percentage of participants | 9vHPV+TDV | 9vHPV |
|---|---|---|
| Pain: Mild | 54.1 | 42.8 |
| Pain: Moderate | 9.5 | 6.5 |
| Pain: Severe | 0.7 | 0 |
| Erythema: Mild | 7.5 | 0 |
| Erythema: Moderate | 0.7 | 0 |
| Swelling: Mild | 3.3 | 0 |
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 | 9vHPV+TDV | 9vHPV |
|---|---|---|
| Headache: Mild | 20.0 | 18.0 |
| Headache: Moderate | 3.0 | 0.7 |
| Headache: Severe | 0.3 | 0 |
| Asthenia: Mild | 16.7 | 12.1 |
| Asthenia: Moderate | 2.0 | 1.0 |
| Asthenia: Severe | 0.3 | 0 |
| Malaise: Mild | 17.7 | 10.5 |
| Malaise: Moderate | 2.0 | 1.3 |
| Malaise: Severe | 0.3 | 0 |
| Myalgia: Mild | 36.1 | 27.8 |
| Myalgia: Moderate | 7.9 | 2.3 |
| Myalgia: Severe | 0.3 | 0.3 |
| Fever: 38.0°C to <38.5°C | 2.0 | 0.3 |
| Fever: 38.5°C to <39.0°C | 0.3 | 0 |
| Fever: 39.0°C to <39.5°C | 0.3 | 0 |
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 | 9vHPV+TDV | 9vHPV |
|---|---|---|
| Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination | 8.8 | 2.6 |
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 | 9vHPV+TDV | 9vHPV |
|---|---|---|
| Percentage of Participants With Serious Adverse Events (SAEs) | 10.1 | 7.2 |
Collected over All-cause mortality and serious adverse events: From first vaccination (Day 1 [Month 0]) through end of study (Day 360 [Month 12]); Non-serious adverse events: Up to 28 days (day of vaccination + 27 days) after each vaccination. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 9vHPV+TDV | 0/307 (0%) | 31/307 (10.1%) | 253/307 (82.4%) |
| 9vHPV | 0/307 (0%) | 22/307 (7.2%) | 223/307 (72.6%) |
| Event | 9vHPV+TDV | 9vHPV |
|---|---|---|
| COVID-19Infections and infestations | 26/307 | 19/307 |
| COVID-19 pneumoniaInfections and infestations | 2/307 | 2/307 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 1/307 | 0/307 |
| BronchitisInfections and infestations | 1/307 | 0/307 |
| Foreign body in gastrointestinal tractInjury, poisoning and procedural complications | 1/307 | 0/307 |
| GastroenteritisInfections and infestations | 1/307 | 0/307 |
| Limb injuryInjury, poisoning and procedural complications | 0/307 | 1/307 |
| Road traffic accidentInjury, poisoning and procedural complications | 0/307 | 1/307 |
| Event | 9vHPV+TDV | 9vHPV |
|---|---|---|
| PainGeneral disorders | 225/307 | 184/307 |
| MyalgiaMusculoskeletal and connective tissue disorders | 135/307 | 93/307 |
| ErythemaSkin and subcutaneous tissue disorders | 92/307 | 57/307 |
| HeadacheNervous system disorders | 71/307 | 59/307 |
| SwellingGeneral disorders | 64/307 | 52/307 |
| MalaiseGeneral disorders | 62/307 | 36/307 |
| AstheniaGeneral disorders | 58/307 | 40/307 |
| FeverGeneral disorders | 8/307 | 1/307 |
| NasopharyngitisInfections and infestations | 3/307 | 0/307 |
| Dermatitis contactSkin and subcutaneous tissue disorders | 2/307 | 0/307 |
Randomized Set included all randomized participants, regardless of whether any dose of the investigational products (IPs) was received.
| Age, Continuous(years) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Mean | 11.1 ± 1.60 | 11.3 ± 1.59 | 11.2 ± 1.59 |
| Sex: Female, Male(Participants) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Female | 150 | 156 | 306 |
| Male | 157 | 151 | 308 |
| Ethnicity (NIH/OMB)(Participants) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 307 | 307 | 614 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 307 | 307 | 614 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Thailand | 307 | 307 | 614 |
| Height(centimeters (cm)) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Mean | 147.68 ± 12.244 | 148.18 ± 11.374 | 147.93 ± 11.809 |
| Weight(kilograms (kg)) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Mean | 44.21 ± 15.913 | 44.37 ± 14.271 | 44.29 ± 15.101 |
| Body Mass Index (BMI)(kilograms per meter square (kg/m^2)) | 9vHPV+TDV | 9vHPV | Total |
|---|---|---|---|
| Mean | 19.78 ± 4.912 | 19.88 ± 4.762 | 19.83 ± 4.834 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting information: Study protocol, Sap, Icf, Csr
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