AzTrials
AzTrials

Dengue FeverPhase 3NCT04313244

Immunogenicity and Safety of Dengue Tetravalent Vaccine (TDV) and Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) in Participants Aged ≥9 to <15 Years

A Phase 3 study testing 9vHPV Vaccine and Dengue Tetravalent Vaccine (TDV) in people with Dengue Fever, run by Takeda at 4 sites in Thailand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 9 to 14 yearsHealthy volunteers can take part
Conditions the study is for
Dengue Fever
What is being tested?
9vHPV Vaccine and Dengue Tetravalent Vaccine (TDV)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
614 participants
Where
4 sitesThailand
Study dates
15 May 2021to 19 Jul 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 to 14 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.
  • Participants who can comply with trial procedures and are available for the duration of follow-up.

Who cannot join

  • Has an elevated oral temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccination.
  • Participants with contraindications, warnings and/or precautions to vaccination with Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) vaccine as specified within the prescribing information.
  • Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease.
  • Known or suspected impairment/alteration of immune function, including:
  • 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).
  • 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).
Show all 21Show fewer
  • Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
  • Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
  • Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
  • Human immunodeficiency virus (HIV) infection or HIV-related disease.
  • Hepatitis B virus infection.
  • Hepatitis C virus infection.
  • Genetic immunodeficiency.
  • Abnormalities of splenic or thymic function.
  • Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  • 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.
  • 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.
  • 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.
  • Previous and planned vaccination (during the trial conduct) against HPV.
  • 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.
  • Has a current or previous infection with a flavivirus such as Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

Trial locations and contacts

4 sites in 1 country.

Thailand4 sites
  • King Chulalongkorn Memorial Hospital

    Bangkok, 10330

  • The Hospital for Tropical Diseases

    Bangkok, 10400

  • Siriraj Hospital

    Bangkoknoi, Khet Bangkok Noi, 10700

  • Thammasat University Hospital

    Pathum Thani, 12121

Other trials in Thailand

About this study

Official title: A Phase 3, Open-Label, Randomized Trial to Investigate the Immunogenicity and Safety of the Co-administration of a Subcutaneous Dengue Tetravalent Vaccine (Live, Attenuated) (TDV) and an Intramuscular Recombinant 9-Valent Human Papillomavirus (9vHPV) Vaccine in Subjects Aged ≥9 to <15 Years in an Endemic Country for Dengue

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.

Read the 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.

Conditions
Dengue Fever
Being tested
9vHPV Vaccine, Dengue Tetravalent Vaccine (TDV)
Keywords
Drug therapy
Medical subject headings
Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 9vHPV VaccineBiological

    9vHPV intramuscular injection

  • Dengue Tetravalent Vaccine (TDV)Biological

    Also called TAK-003

    TDV subcutaneous injection

Study groups in NCT04313244
Study groupRoleWhat they receive
9vHPV+TDVExperimentalParticipants 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).
Receives: Biological: 9vHPV Vaccine; Biological: Dengue Tetravalent Vaccine (TDV)
9vHPVExperimentalParticipants 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).
Receives: Biological: 9vHPV Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 210 (Month 7)

Secondary outcomes (8)
  1. 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.

    Measured: Day 210 (Month 7)

  2. 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.

    Measured: Day 120 (Month 4)

  3. 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.

    Measured: Day 120 (Month 4)

  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.

    Measured: Day 120 (Month 4)

  5. 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.

    Measured: Up to 7 days (Day of vaccination + 6 subsequent days) after each vaccination

  6. 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.

    Measured: Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination

  7. 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.

    Measured: Up to 28 days (Day of vaccination + 27 subsequent days) after each vaccination

  8. 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.

    Measured: From first vaccination (Day 1 [Month 0]) through end of study (Day 360 [Month 12])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2020
  2. Study start15 May 2021
  3. Primary completion21 Feb 2022
  4. Study completion19 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
614 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04313244
Sponsor's protocol ID
DEN-308
Other IDs
2022-003339-24
Status last verified
Jan 2024
First submitted
16 Mar 2020
Last updated
7 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

Publications

  • El Hindi T, Anugulruengkitt S, Lapphra K, Limkittikul K, Tangsathapornpong A, Galindo CM, Hellwig M, Roubinis N, Schuring R, Biswal S, Folschweiller N. Immunogenicity and safety of the live-attenuated tetravalent dengue vaccine (TAK-003) co-administered with recombinant 9-valent human papillomavirus vaccine. Vaccine. 2025 Oct 24;65:127786. doi: 10.1016/j.vaccine.2025.127786. Epub 2025 Oct 6.

    PubMed 41058426
  • El Hindi T, Anugulruengkitt S, Lapphra K, Limkittikul K, Tangsathapornpong A, Galindo-Tsoukas C, Hellwig M, Roubinis N, Schuring R, Biswal S, Folschweiller N. Immunogenicity and safety of the live-attenuated tetravalent dengue vaccine (TAK-003) co-administered with recombinant 9-valent human papillomavirus vaccine. Vaccine. 2025 Aug 30;62:127558. doi: 10.1016/j.vaccine.2025.127558. Epub 2025 Jul 31.

    PubMed 40749348
  • Rauscher M, Youard Z, Faccin A, Patel SS, Pang H, Zent O. Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine. Expert Rev Vaccines. 2025 Dec;24(1):221-229. doi: 10.1080/14760584.2025.2480297. Epub 2025 Mar 27.

    PubMed 40099800

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 9vHPV Vaccine and Dengue Tetravalent Vaccine (TDV) in people with Dengue Fever, run by Takeda at 4 sites in Thailand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 (time frame: Day 210 (Month 7)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04313244, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in