A Study of Dengue Tetravalent Vaccine (TDV) in Adults (Age 45 to 60 and >60 to 79 Years)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled (Older Adults, Aged >60 to 79 Years) and Open-Label (Adults, Aged 45 to 60 Years), Multicenter Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (TDV) Administered Subcutaneously to Adults and Older Adults With or Without Comorbidities in Endemic Areas for Dengue

Dengue fever is caused by an infection with the dengue virus. Vaccination with Dengue Tetravalent Vaccine (TDV) can help prevent dengue fever. Researchers have seen that dengue fever now also happens more often in elderly persons. The main aim of this study is to learn more about the side effects of TDV in adult (45 - 60 years) and elderly (60 - 79 years) persons and about TDV's ability to create an immune response in adult and elderly persons. Another aim is to learn about the side effects of TDV in adult and elderly persons in endemic countries who have one or more additional medical conditions (called comorbidities) such as diabetes mellitus, hypertension or a chronic kidney condition.

In this study, participants will receive 2 vaccinations with TDV (the second 3 months after the first).

During the study, participants will visit their study clinic 5 times.

Study Overview

• Status: Recruiting
• Conditions: Dengue Fever
• Intervention / Treatment: Biological: TDV; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1427CEA
    • Recruiting
    • Fundacion Huesped - PPDS
    • Contact: Site Contact; Phone Number: +5411 2120 9999; Email: florencia.cahn@huesped.org.ar
    • Principal Investigator: Florencia Cahn
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40444-130
      • Recruiting
      • Associacao Obras Sociais Irma Dulce Hospital Santo Antonio
      • Principal Investigator: Edson Moreira Junior
      • Contact: Site Contact; Phone Number: (557) 131-7623 43; Email: edson@bahia.fiocruz.br
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Recruiting
      • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
      • Contact: Site Contact; Phone Number: +55 17 3201-5000; Email: mauricio.nogueira@edu.famerp.br
      • Principal Investigator: Mauricio Lacerda Nogueira
• Singapore
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital
    • Contact: Site Contact; Phone Number: (656) 357-8010; Email: po_ying_chia@ncid.sg
    • Principal Investigator: Po Ying Chia
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital (SGH)
    • Principal Investigator: Jenny Low
    • Contact: Site Contact; Phone Number: (656) 321-3479; Email: jenny.low@singhealth.com.sg
• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Recruiting
      • Ramathibodi hospital
      • Contact: Site Contact; Phone Number: (662) 201-0033; Email: sasisopin.kie@mahidol.ac.th
      • Principal Investigator: Sasisopin Kiertiburanakul
  • Krung Thep Maha Nakhon-Bangkok
    • Ratchathewi, Krung Thep Maha Nakhon-Bangkok, Thailand, 10400
      • Recruiting
      • Hospital For Tropical Diseases
      • Principal Investigator: Punnee Pitisuttithum
      • Contact: Site Contact; Phone Number: (662) 643-5599; Email: punnee.pit@mahidol.ac.th

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participant is aged 45 to 79 years at the time of entry into the trial.
2. Participant is male or female.
3. Participant is in good health or has a medical diagnosis of one or more of diabetes mellitus, hypertension, or chronic kidney disease (that is, comorbidities) and are medically stable in the opinion of the investigator at the time of entry into the trial, as determined by medical history and targeted physical examination. Medically stable is defined as no change in diagnoses or chronic medications (dose or class) for medical reasons in the 3 months prior to participating in the trial.
4. Participant has signed and dated a written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, and after the nature of the trial has been explained according to local regulatory requirements.
5. Participant can comply with trial procedures and is available for the duration of follow-up.

Exclusion Criteria:

1. Participant has contraindication(s), warning(s), and/or precaution(s) applicable to vaccination with TDV as specified in the Investigator's Brochure and/or approved product label (as applicable) in the participating country.
2. Participant has a known hypersensitivity or allergy to any of the TDV or placebo components (including excipients).
3. Participant has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, could interfere with the participant's ability to take part in the trial.
4. Participant has a history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (example, Guillain-Barré syndrome).
5. Participant has an illness, or history of any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participant due to involvement in this trial.

6. Participant has a known or suspected altered immunocompetence, including:

   1. Chronic administration of oral and/or parenteral steroids at doses considered sufficiently immunosuppressive (example, greater than or equal to [>=] 2 milligram per kilogram [mg/kg] body weight prednisone [or equivalent] for >=14 consecutive days, or >=20 milligram per day [mg/day] prednisone [or equivalent] administered for >=14 consecutive days) within 60 days prior to Day 1 (month [M0]) (note: use of corticosteroids by inhaled, intranasal, intra-articular, bursal, tendon injection, or topical routes is allowed).
   2. Receipt of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
   3. Receipt of immunostimulants within 60 days prior to Day 1 (M0).
   4. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
   5. Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
   6. Hepatitis B virus infection.
   7. Hepatitis C virus infection.
   8. Genetic immunodeficiency.
7. Participant has known or suspected abnormalities of splenic or thymic function.
8. Participant has a known bleeding diathesis, or any condition/medication that may be associated with a prolonged bleeding time.
9. Participant has a serious chronic or progressive disease deemed to be preclusive to trial entry, that is, not medically stable according to the judgment of the investigator.
10. Participant has previously received a vaccination against dengue virus (investigational or licensed).
11. Participant had a clinically significant active infection (as assessed by the investigator) or body temperature >38.0 degree Celsius (>100.4 degree Fahrenheit) within 3 days of intended TDV or placebo administration.
12. Participant has used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis vs treatment) must be documented. Trial entry must be delayed to allow for a full 24 hours to have passed since the last use of antipyretics and/or analgesic medications.
13. Participant has a history of substance or alcohol abuse within the past 2 years.
14. Female participants who are pregnant (that is, a positive or indeterminate pregnancy test).
15. Female participants who are breastfeeding.
16. Female participants of childbearing potential who are sexually active and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (M0).
17. Female participants of childbearing potential who are sexually active and who refuse to use an acceptable contraceptive method up to 6 weeks post final vaccination on Day 90 (M3). In addition, they must also be advised not to donate ova during this period.

18. Participant has received any of the following:

    1. A licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to TDV or placebo administration on Day 1 (M0). This includes co-administration with routine vaccines.
    2. A coronavirus vaccine within 14 days prior to TDV or placebo administration.
    3. A vaccine authorized for emergency use within 28 days prior to TDV or placebo administration.
19. Participant is scheduled to receive any other vaccine within 28 days after TDV or placebo administration.
20. Participant is participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intending to participate in another clinical trial at any time during the conduct of this trial.
21. Participant has taken part in any clinical trial of a dengue or other flavivirus (example, West Nile virus) candidate vaccine, except if it is known that the participant received placebo in those trials.
22. Participant or their first-degree relatives are involved in the trial conduct.
23. Participant identified as an employee of the investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial center.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Tetravalent Dengue Vaccine (TDV) 0.5 mL; Participants with the age group greater than (>) 60 to 79 years will receive TDV, 0.5 mL subcutaneous (SC) injections, on Day 1 and Day 90.	Biological: TDV; TDV SC injection.; Other Names: TAK-003
Placebo Comparator: Cohort 1: Placebo; Participants with the age group >60 to 79 years will receive placebo (normal saline), 0.5 mL SC injections, on Day 1 and Day 90.	Other: Placebo; Placebo SC injection.
Experimental: Cohort 2: TDV 0.5 mL; Participants with the age group 45 to 60 years will receive TDV, 0.5 mL SC injection, on Day 1 and Day 90.	Biological: TDV; TDV SC injection.; Other Names: TAK-003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 1	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medical product (IMP); it does not necessarily have to have a causal relationship with IMP administration. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration.	Within 7 days post-vaccination at Day 1
Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 90	Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration.	Within 7 days post-vaccination at Day 90
Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1	Solicited systemic AEs include fever (body temperature greater than or equal to [>=] 38 degree Celsius [C], asthenia, malaise, headache, and myalgia.	Within 14 days post-vaccination at Day 1
Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 90	Solicited systemic AEs include fever (body temperature >= 38 degree (C), asthenia, malaise, headache, and myalgia.	Within 14 days post-vaccination at Day 90
Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 1	Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 7 days post-vaccination at Day 1
Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 90	Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 7 days post-vaccination at Day 90
Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 1	Solicited systemic AEs include fever (body temperature >= 38 degree (C), asthenia, malaise, headache, and myalgia. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 14 days post-vaccination at Day 1
Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 90	Solicited systemic AEs include fever (body temperature >= 38 degree (C), asthenia, malaise, headache, and myalgia. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 14 days post-vaccination at Day 90
Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 1	An unsolicited AE is any AE reported by the participant that is not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting a solicited AE (that is, 7 days and 14 days in total including the day IMP administration).	Within 28 days post-vaccination at Day 1
Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 90	An unsolicited AE is any AE reported by the participant that is not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting a solicited AE (that is, 7 days and 14 days in total including the day of IMP administration).	Within 28 days post-vaccination at Day 90
Percentage of Participants with a Serious Adverse Event (SAE)	An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event.	From first vaccination on Day 1 through the end of trial (up to Day 270)
Geometric Mean Titers (GMTs) of Neutralizing Antibodies by Microneutralization Test (MNT) for Each of the 4 Dengue Virus Serotypes at Day 120	GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes in all participants. The 4 dengue virus serotypes are dengue virus (DENV)-1, DENV-2, DENV-3 and DENV-4.	At Day 120

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Solicited Local (Injection Site) AEs Within 7 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities)	Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration.	Within 7 days post-vaccination at Day 1 and Day 90
Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities)	Solicited systemic AEs include fever (body temperature >= 38 degree (C), asthenia, malaise, headache, and myalgia.	Within 14 days post-vaccination at Day 1 and Day 90
Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 days Post Vaccination at Day 1 and Day 90 (With Comorbidities)	Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. All solicited AEs at the injection site will be considered related to the study vaccine administration. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 7 days post-vaccination at Day 1 and Day 90
Percentage of Participants with Solicited Systemic AEs by Severity (With Comorbidities)	Solicited systemic AEs include fever (body temperature >= 38 degree (C), asthenia, malaise, headache, and myalgia. The AEs will be graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe.	Within 14 days post-vaccination at Day 1 and Day 90
Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination (With Comorbidities)	An unsolicited AE is any AE reported by the participant that is not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting a solicited AE (that is, 7 days and 14 days in total including the day IMP administration).	Within 28 days post-vaccination at Day 1 and Day 90
Percentage of Participants with a SAE (With Comorbidities)	An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event.	From first vaccination on Day 1 through the end of trial (up to Day 270)
Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 dengue serotypes in all participants. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90 and Day 270
Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes (With Comorbidities)	GMTs of neutralizing antibodies will be measured by MNT50 for each of the 4 dengue serotypes. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90, Day 120 and Day 270
Seropositivity Rate for Each of the 4 Dengue Virus Serotypes	Seropositivity rate is defined as the percentage of participants with MNT titer >=10 against each of the four dengue virus serotypes in all participants. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90, Day 120 and Day 270
Seropositivity Rate for Each of the 4 Dengue Virus Serotypes (With Comorbidities)	Seropositivity rate is defined as the percentage of participants with MNT titer >=10 against each of the four dengue virus serotypes. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90, Day 120 and Day 270
Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes	Seropositivity rate is defined as the percentage of participants with MNT titer >=10 against multiple (2, 3, or 4) dengue virus serotypes in all participants. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90, Day 120 and Day 270
Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes (With Comorbidities)	Seropositivity rate is defined as the percentage of participants with MNT titer >=10 against multiple (2, 3, or 4) dengue virus serotypes. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 30, Day 90, Day 120 and Day 270

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
• Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): April 14, 2027

Study Registration Dates

• First Submitted: August 29, 2024
• First Submitted That Met QC Criteria: August 29, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Vaccination
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: DEN-321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No