Dengue FeverPhase 2NCT02302066

Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

A Phase 2 study testing Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in people with Dengue Fever, run by Takeda at 3 sites in 3 countries.

Completed

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

Official record

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Trial summary

The purpose of this study is to assess the humoral immune responses to three different dose schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) administered subcutaneously in healthy participants between 2 and <18 years of age living in dengue endemic countries. Read more about this study

Who is it for?: Ages 2 to 17 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever
What is being tested?: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,800 participants
Where: 3 sitesin 3 countries
Study dates: 5 Dec 2014to 18 Feb 2019
Phase: Phase 2
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 2 to 17 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Is aged 2 to <18 years, at the time of enrolment.
Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and clinical judgment of the investigator.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form (and assent form, where required) and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
Can comply with trial procedures and are available for the duration of follow-up.

Who cannot join

Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrolment. Trial entry should be delayed until the illness has improved.
Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components; b. Female participants who are pregnant or breastfeeding; c. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin-dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome); d. Known or suspected impairment/alteration of immune function, including: i. 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 (use of inhaled, intranasal, or topical corticosteroids is allowed); ii. 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; iii. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial; iv. Receipt of immunostimulants within 60 days prior to Day 1; v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months preceding (first) vaccination; vi. Human immunodeficiency virus (HIV) infection or HIV-related disease; vii. Genetic immunodeficiency.
Individuals 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 investigational vaccine administration.
Individuals participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
Individuals who are first degree relatives of individuals involved in trial conduct.
If female of childbearing potential, sexually active, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry: a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal (for at least 2 years), bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy; b. Acceptable birth control methods are defined as one or more of the following: i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; iii. Intrauterine device (IUD); iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
If female of childbearing potential, sexually active and refuses to use an "acceptable contraceptive method" through to 6 weeks after the last dose of investigational vaccine.
Individuals who participated in a previous dengue vaccine trial.

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

Dominican Republic1 site

Hospital Maternidad Nuestra Senora de la Altagracia
Santo Domingo, Distrito Nacional Santo Domingo, 10204

Other trials in Dominican Republic

Panama1 site

Centro De Vacunacion Internacional, S.A.(CEVAXIN)
Panama City, 10662

Other trials in Panama

Philippines1 site

Dela Salle Health Sciences Institute
Dasmariñas, Cavite, 4114

Other trials in Philippines

About this study

Official title: A Phase II, Double-Blind, Controlled Trial to Assess the Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Subjects Aged Between 2 and <18 Years and Living in Dengue Endemic Countries in Asia and Latin America

Read the detailed description

The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV) which was administered in 3 different dosing schedules to participants aged from 2 to 17 years resident in dengue endemic countries. This study looked at the titers of antibodies to dengue fever elicited in people who received TDV.

The study randomized 1800 healthy participants. Participants were randomly assigned to one of the four treatment groups in a 1:2:5:1 ratio-which remained undisclosed to the participant and study doctor during the study (unless there was an urgent medical need):

Group 1 - TDV 0.5 mL subcutaneous (SC) injection Days 1 and 91
Group 2 - TDV 0.5 mL SC injection Day 1
Group 3 - TDV 0.5 mL SC injection Days 1 and 365
Group 4 - Placebo (dummy SC) - this is a liquid that looks like the study drug but has no active ingredient

A total of 600 participants were planned to be randomly included in immunogenicity analyses (approximately 100 participants planned in each of Group 1 and Group 4, and 200 participants planned in each of Group 2 and Group 3).

In order to keep the treatment arms undisclosed to the participant and the doctor, participants received a placebo injection at any study visit where TDV was not being administered (Days 1 and/or 91 and/or 365).

Participants were asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 28 days after each vaccination.

This multi-center trial was conducted in Asia and Latin America. Participants were followed for 48 months with 10 protocol-scheduled visits for participants included in the planned immunogenicity subset of approximately 600 subjects and 7 protocol-scheduled visits for subjects not included in the immunogenicity subset.

Conditions: Dengue Fever
Being tested: Takeda's Tetravalent Dengue Vaccine Candidate (TDV), TDV Placebo
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.

Takeda's Tetravalent Dengue Vaccine Candidate (TDV)Biological
TDV subcutaneous injection
TDV PlaceboBiological
Placebo-matching vaccine

Study groups in NCT02302066
Study group	Role	What they receive
Group 1 (TDV 2-Dose)	Experimental	Takeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 91. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 365. Receives: Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); Biological: TDV Placebo
Group 2 (TDV 1-Dose)	Experimental	Takeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Day 1. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 91 and 365. Receives: Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); Biological: TDV Placebo
Group 3 (TDV 1-Dose + Booster)	Experimental	Takeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 365. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 91. Receives: Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); Biological: TDV Placebo
Group 4 (Placebo Control)	Placebo comparator	Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 1, 91 and 365. Receives: Biological: TDV Placebo

What is being measured

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

Geometric Mean Titers (GMTs) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset
GMTs of neutralizing antibodies were measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Data reported for up to Month 48 was collected at Months 1, 3, 6, 12, 13, 18, 24, 36 and 48.
Measured: Up to Month 48

Secondary outcomes (8)

Seropositivity Rates For Each of the 4 Dengue Serotypes for Participants in the Immunogenicity Subset
Seropositivity rate, defined as the percentage of participants seropositive, was derived from the titers of dengue-neutralizing antibodies. Seropositivity defined as a reciprocal neutralizing titer ≥10 (for each serotype). The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Measured: Months 1, 3, 6, 12, 13, 18, 24, 36, and 48
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
Solicited local injection included pain, erythema at injection site, and swelling at injection site. They were collected using a diary and graded as [Grade 0 (no pain), 1 (mild: minor reaction to touch), 2 (moderate: cries/protests on touch) and 3 (severe: cries when limb is moved/spontaneously painful)]. Erythema and Swelling at injection site were graded as Grade 0 (<10 mm), 1 (mild: ≥10 - ≤ 20 mm), 2 (moderate: > 20 - ≤ 40 mm) and 3 (severe: > 40 mm).
Measured: Within 7 days after each vaccination
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
Solicited local injection site reactions were collected by participant diary and graded as [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 at injection site were graded as Grade 0 (<25 mm), 1 (mild: ≥25 - ≤ 50 mm), 2 (moderate: > 50 - ≤ 100 mm).
Measured: Within 7 days after each vaccination
Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
Solicited systemic AEs were collected within 14 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it.
Measured: Within 14 days after each vaccination
Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
Solicited systemic AEs were collected by participants within 14 days after vaccination and included headache, asthenia, malaise, myalgia and fever. Severity scales for headache were none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents normal activity with or without treatment. Severity scales for others were none, mild: no interference with daily activity, moderate: interference with daily activity and severe: prevents daily activity. A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it.
Measured: Within 14 days after each vaccination
Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Immunogenicity Subset Following Each Vaccination
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Measured: Within 28 days after each vaccination
Percentage of Participants With Serious Adverse Events (SAEs)
An SAE was 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 due to other reasons than the above-mentioned criteria.
Measured: From first vaccination through end of study (Day 1460)
Percentage of Participants With Febrile Episodes of Virologically Confirmed Dengue With Onset 30 Days Post-first Vaccination
Participants with febrile illness (defined as temperature ≥ 38°C on 2 consecutive days) were evaluated for dengue. A dengue infection was considered virologically confirmed by either positive polymerase chain reaction (PCR) or NS1 enzyme-linked immunosorbent assay (ELISA). Virologically confirmed dengue with onset 30 days after first vaccination within each group.
Measured: From 30 days post-first vaccination through end of study (Day 1460)

Timeline

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

5 Dec 201418 Feb 2019

First posted26 Nov 2014 (estimated)
Study start5 Dec 2014
Primary completion18 Feb 2019
Study completion18 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Dengue FeverStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,800 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02302066
Sponsor's protocol ID: DEN-204
Other IDs: PHRR140804-000219, U1111-1154-2475, 2018-003978-28, 2018
Status last verified: Feb 2020
First submitted: 24 Nov 2014
Last updated: 24 Feb 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Takeda makes patient/subject-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

Gottardo R, Dean H, Nascimento EJM, Tricou V, Sharma M. Beyond neutralization: A comprehensive framework for evaluating humoral immunity induced by a live-attenuated tetravalent dengue vaccine. Vaccine. 2026 Aug 13;88:128929. doi: 10.1016/j.vaccine.2026.128929. Epub 2026 Jul 21.
PubMed 42480195
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
Tricou V, Gottardo R, Egan MA, Clement F, Leroux-Roels G, Saez-Llorens X, Borkowski A, Wallace D, Dean HJ. Characterization of the cell-mediated immune response to Takeda's live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting. Vaccine. 2022 Feb 16;40(8):1143-1151. doi: 10.1016/j.vaccine.2022.01.016. Epub 2022 Jan 22.
PubMed 35078666
Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
PubMed 33534885
Tricou V, Saez-Llorens X, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Saldana de Suman O, Montenegro N, DeAntonio R, Mazara S, Vargas M, Mendoza D, Rauscher M, Brose M, Lefevre I, Tuboi S, Borkowski A, Wallace D. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial. Lancet. 2020 May 2;395(10234):1434-1443. doi: 10.1016/S0140-6736(20)30556-0. Epub 2020 Mar 17.
PubMed 32197107
Saez-Llorens X, Tricou V, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Mazara S, Vargas M, Brose M, Rauscher M, Tuboi S, Borkowski A, Wallace D. Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2018 Feb;18(2):162-170. doi: 10.1016/S1473-3099(17)30632-1. Epub 2017 Nov 6.
PubMed 29122463
Saez-Llorens X, Tricou V, Yu D, Rivera L, Tuboi S, Garbes P, Borkowski A, Wallace D. Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2017 Jun;17(6):615-625. doi: 10.1016/S1473-3099(17)30166-4. Epub 2017 Mar 30.
PubMed 28365225

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Dengue Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Double-Blind, Controlled Trial to Assess the Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Subjects Aged Between 2 and <18 Years and Living in Dengue Endemic Countries in Asia and Latin America
ClinicalTrials.gov ID: NCT02302066
Acronym / sponsor ID: DEN-204
Conditions: Dengue Fever
Keywords: Drug therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,800 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 5 Dec 2014 (actual)
Primary completion: 18 Feb 2019 (actual)
Study completion: 18 Feb 2019 (actual)
First posted: 26 Nov 2014 (estimated)
Results: Posted 24 Feb 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Group 1 - TDV 0.5 mL subcutaneous (SC) injection Days 1 and 91
Group 2 - TDV 0.5 mL SC injection Day 1
Group 3 - TDV 0.5 mL SC injection Days 1 and 365
Group 4 - Placebo (dummy SC) - this is a liquid that looks like the study drug but has no active ingredient

Participants were asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 28 days after each vaccination.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Group 1 (TDV 2-Dose)	Experimental	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV), Biological: TDV PlaceboTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 91. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 365.
Group 2 (TDV 1-Dose)	Experimental	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV), Biological: TDV PlaceboTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Day 1. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 91 and 365.
Group 3 (TDV 1-Dose + Booster)	Experimental	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV), Biological: TDV PlaceboTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 365. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 91.
Group 4 (Placebo Control)	Placebo comparator	Biological: TDV PlaceboPlacebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 1, 91 and 365.

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (4 listed)

Is aged 2 to <18 years, at the time of enrolment.
Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and clinical judgment of the investigator.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form (and assent form, where required) and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
Can comply with trial procedures and are available for the duration of follow-up.

Key exclusion criteria (8 listed)

Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrolment. Trial entry should be delayed until the illness has improved.
Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components; b. Female participants who are pregnant or breastfeeding; c. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin-dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome); d. Known or suspected impairment/alteration of immune function, including: i. 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 (use of inhaled, intranasal, or topical corticosteroids is allowed); ii. 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; iii. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial; iv. Receipt of immunostimulants within 60 days prior to Day 1; v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months preceding (first) vaccination; vi. Human immunodeficiency virus (HIV) infection or HIV-related disease; vii. Genetic immunodeficiency.
Individuals 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 investigational vaccine administration.
Individuals participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
Individuals who are first degree relatives of individuals involved in trial conduct.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Takeda's Tetravalent Dengue Vaccine Candidate (TDV)TDV subcutaneous injection	Biological	Group 1 (TDV 2-Dose), Group 2 (TDV 1-Dose), Group 3 (TDV 1-Dose + Booster)
TDV PlaceboPlacebo-matching vaccine	Biological	Group 1 (TDV 2-Dose), Group 2 (TDV 1-Dose), Group 3 (TDV 1-Dose + Booster), Group 4 (Placebo Control)

Primary outcome

Geometric Mean Titers (GMTs) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset
Time frame: Up to Month 48
GMTs of neutralizing antibodies were measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Data reported for up to Month 48 was collected at Months 1, 3, 6, 12, 13, 18, 24, 36 and 48.

8 secondary outcomes

Seropositivity Rates For Each of the 4 Dengue Serotypes for Participants in the Immunogenicity Subset
Time frame: Months 1, 3, 6, 12, 13, 18, 24, 36, and 48
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
Time frame: Within 7 days after each vaccination
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
Time frame: Within 7 days after each vaccination
Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Infant/Toddler Following Each Vaccination
Time frame: Within 14 days after each vaccination
Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) by Severity in the Immunogenicity Subset of Adult/Children Following Each Vaccination
Time frame: Within 14 days after each vaccination
Percentage of Participants With Any Unsolicited Adverse Events (AEs) in the Immunogenicity Subset Following Each Vaccination
Time frame: Within 28 days after each vaccination
Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: From first vaccination through end of study (Day 1460)
Percentage of Participants With Febrile Episodes of Virologically Confirmed Dengue With Onset 30 Days Post-first Vaccination
Time frame: From 30 days post-first vaccination through end of study (Day 1460)

Results and safety

Results posted to the registry on 24 Feb 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1 (TDV 2-Dose)	201	168
Group 2 (TDV 1-Dose)	398	323
Group 3 (TDV 1-Dose + Booster)	1,002	830
Group 4 (Placebo Control)	199	158

Primary outcome: Geometric Mean Titers (GMTs) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset

Time frame: Up to Month 48. Geometric mean (95% Confidence Interval). Unit: titer

Measure	Group 1 (TDV 2-Dose) n = 83	Group 2 (TDV 1-Dose) n = 171	Group 3 (TDV 1-Dose + Booster) n = 174	Group 4 (Placebo Control) n = 81
DENV-1, Day 28 (Month 1)	768.2 (498.7 to 1183.4)	999.7 (723.6 to 1381.2)	920.9 (689.4 to 1230.1)	60.7 (31.8 to 116.0)
DENV-2, Day 28 (Month 1)	4329.7 (2847.6 to 6583.2)	4219.3 (3118.9 to 5708.1)	3572.2 (2674.6 to 4771.2)	75.0 (39.6 to 141.8)
DENV-3, Day 28 (Month 1)	216.1 (124.7 to 374.6)	352.8 (237.5 to 524.2)	363.6 (249.8 to 529.1)	45.8 (25.9 to 81.1)
DENV-4, Day 28 (Month 1)	199.2 (130.0 to 305.2)	317.3 (232.2 to 433.5)	260.4 (195.0 to 347.7)	24.8 (16.2 to 38.0)
DENV-1, Day 91 (Month 3)	422.3 (256.7 to 695.0)	684.2 (491.4 to 952.8)	708.9 (522.6 to 961.6)	64.6 (33.8 to 123.4)
DENV-2, Day 91 (Month 3)	1810.1 (1311.1 to 2499.2)	2216.9 (1750.8 to 2807.2)	1709.6 (1370.4 to 2132.7)	76.0 (40.1 to 144.3)
DENV-3, Day 91 (Month 3)	140.8 (83.8 to 236.6)	250.8 (174.5 to 360.6)	251.9 (175.7 to 361.2)	39.3 (22.6 to 68.2)
DENV-4, Day 91 (Month 3)	122.9 (77.6 to 194.6)	170.8 (122.6 to 237.8)	147.0 (108.4 to 199.2)	23.4 (14.9 to 36.9)

Population analysed: Per Protocol Set (PPS): All participants who received at least 1 dose of trial vaccine, who had a valid pre-dose and at least 1 valid post-dose measurement for immunogenicity and no major protocol violations. PPS included only participants from Immunogenicity Subset. Number analyzed are participants with data available at the given timepoint.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality and Serious adverse events: From first vaccination (Day 1) through end of study (Day 540); Other adverse events: From any vaccination (Day 1, Day 91, and Day 365) up to 28 days post vaccination.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1 (TDV 2-Dose)	10 of 200 (5%)	17 of 91 (18.7%)	0 of 200
Group 2 (TDV 1-Dose)	18 of 398 (4.5%)	43 of 187 (23%)	1 of 398
Group 3 (TDV 1-Dose + Booster)	65 of 998 (6.5%)	41 of 191 (21.5%)	1 of 998
Group 4 (Placebo Control)	10 of 198 (5.1%)	22 of 93 (23.7%)	0 of 198

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42480195Gottardo R, Dean H, Nascimento EJM, Tricou V, Sharma M. Beyond neutralization: A comprehensive framework for evaluating humoral immunity induced by a live-attenuated tetravalent dengue vaccine. Vaccine. 2026 Aug 13;88:128929. doi: 10.1016/j.vaccine.2026.128929. Epub 2026 Jul 21.
Derived from this study: PubMed 40099800Rauscher 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.
Derived from this study: PubMed 35078666Tricou V, Gottardo R, Egan MA, Clement F, Leroux-Roels G, Saez-Llorens X, Borkowski A, Wallace D, Dean HJ. Characterization of the cell-mediated immune response to Takeda's live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting. Vaccine. 2022 Feb 16;40(8):1143-1151. doi: 10.1016/j.vaccine.2022.01.016. Epub 2022 Jan 22.
Derived from this study: PubMed 33534885Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
Derived from this study: PubMed 32197107Tricou V, Saez-Llorens X, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Saldana de Suman O, Montenegro N, DeAntonio R, Mazara S, Vargas M, Mendoza D, Rauscher M, Brose M, Lefevre I, Tuboi S, Borkowski A, Wallace D. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial. Lancet. 2020 May 2;395(10234):1434-1443. doi: 10.1016/S0140-6736(20)30556-0. Epub 2020 Mar 17.
Derived from this study: PubMed 29122463Saez-Llorens X, Tricou V, Yu D, Rivera L, Jimeno J, Villarreal AC, Dato E, Mazara S, Vargas M, Brose M, Rauscher M, Tuboi S, Borkowski A, Wallace D. Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2018 Feb;18(2):162-170. doi: 10.1016/S1473-3099(17)30632-1. Epub 2017 Nov 6.
Derived from this study: PubMed 28365225Saez-Llorens X, Tricou V, Yu D, Rivera L, Tuboi S, Garbes P, Borkowski A, Wallace D. Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study. Lancet Infect Dis. 2017 Jun;17(6):615-625. doi: 10.1016/S1473-3099(17)30166-4. Epub 2017 Mar 30.
Individual participant dataSharing planned: Yes. Takeda makes patient/subject-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Program Medical Director study director

Takeda

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in people with Dengue Fever, run by Takeda at 3 sites in 3 countries.

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 4 inclusion and 8 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 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Dominican Republic, Panama, Philippines. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 24 Feb 2020). 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) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset (time frame: Up to Month 48). 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 NCT02302066, which also lists 7 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 24 Feb 2020.