Dengue FeverPhase 2NCT03746015

Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults

A Phase 2 study testing TDV in people with Dengue Fever, run by Takeda at 2 sites in United States.

Completed

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

Trial summary

The purpose of this study is to assess the neutralizing antibody response against each dengue serotype post-vaccination. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever
What is being tested?: TDV
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 2 sitesUnited States
Study dates: 28 Dec 2018to 1 Mar 2021
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 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Who are 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.
Group 1 only: immunologically naïve to dengue, Zika, Yellow Fever (YF), Japanese Encephalitis (JE), West Nile (WN) (based on negative results for detection of anti-DENV, anti-Zika, anti-YF, anti-JE, anti-WN antibodies) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days [10 weeks] prior to Day 1 [Month 0]).
Group 2 only: serology consistent with primary infection with either DENV-1 or DENV-3 (defined as detectable neutralizing antibodies against DENV-1 or DENV-3 only, or titers for DENV-1 or DENV-3 ≥4-times higher than titers for the 2 other dengue serotypes) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days [10 weeks] prior to Day 1 [Month 0]).

Who cannot join

Has clinically active significant infection (as assessed by the investigator) or body temperature ≥38°C (100.4°F) within 3 days of the intended date of vaccination.
Has history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
Known or suspected impairment/alteration of immune function including:
Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or ≥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 and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0).
Administration of immunoglobulins and/or any blood products within 3 months prior to Day 1 (Month 0) or planned administration during the trial.

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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).
Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
Hepatitis C virus infection.
Genetic immunodeficiency.
Has planned vaccination (during the trial conduct) against any non-dengue flavivirus (eg, Zika, YF, JE, WN, tick-borne encephalitis, or Murray-Valley encephalitis).
Planned travel (during the trial conduct) to any area endemic for dengue.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Optimal Research
Peoria, Illinois, 61614
Oregon Health and Science University
Portland, Oregon, 97239

Other trials in United States

About this study

Official title: An Open-Label, Phase 2 Trial to Investigate the Humoral and Cell-Mediated Immune Responses and Safety of a Tetravalent Dengue Vaccine Candidate (TDV) Administered Subcutaneously in Flavivirus-Naïve and Dengue-Immune Healthy Adults

The purpose of this study is to assess the neutralizing antibody response against each dengue serotype post-vaccination.

Read the detailed description

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study will look at the immunogenicity and safety of TDV in flavivirus-naïve and dengue-immune adults.

The study will enroll approximately 44 patients. Participants will be categorized into two groups based on results from serological testing performed by the trial center outside the scope of this trial (up to 70 days [10 weeks] prior to Day 1 [Month 0]):

Group 1: Flavivirus-Naïve Participants Group 2: Dengue-Immune Participants

All participants will receive subcutaneous injection of TDV on Day 1 (Month 0) and Day 90 (Month 3).

This trial will be conducted in the United States. The overall time to participate in this study is 12 months. Participants will make multiple visits to the clinic, and 9 months after last dose of study drug for a follow-up assessment.

Conditions: Dengue Fever
Being tested: TDV
Keywords: Vaccine
Medical subject headings: Dengue

What participants receive

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

TDVBiological
TDV subcutaneous injection comprised of 1 molecularly characterized, attenuated dengue virus strain, and 3 chimeric dengue virus strains with potencies of not less than 3.3, 2.7, 4.0, and 4.5 log10 plaque forming units (PFU) per dose of TDV-1, TDV-2, TDV-3, and TDV-4, respectively.

Study groups in NCT03746015
Study group	Role	What they receive
TDV: Flavivirus-naïve	Experimental	Tetravalent Dengue Vaccine (TDV) 0.5 mL, subcutaneous (SC) injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants who were flavivirus-naïve were included in this group. Receives: Biological: TDV
TDV: DENV Immune: DENV-1 Positive	Experimental	TDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by wild type dengue virus serotype-1 (DENV-1) were included in this group. Receives: Biological: TDV
TDV: DENV Immune: DENV-3 Positive	Experimental	TDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by DENV-3 were included in this group. Receives: Biological: TDV

What is being measured

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

Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test 50% (MNT50).
Measured: Day 15
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 30 (Month 1)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 30 (Month 1)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 60 (Month 2)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 60 (Month 2)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 90 (Month 3)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 90 (Month 3)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 105
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 105
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 120 (Month 4)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 120 (Month 4)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 150 (Month 5)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 150 (Month 5)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 180 (Month 6)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 180 (Month 6)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 270 (Month 9)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 270 (Month 9)
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 360 (Month 12)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
Measured: Day 360 (Month 12)

Secondary outcomes (12)

Percentage of Participants With Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Responses to Tetravalent Dengue Vaccine (TDV)
IFN-γ ELISpot response >3 times higher compared with baseline (no peptide) and ≥5 spots per 10^6 peripheral blood mononuclear cells (PBMCs) was defined as cellular immune response. Cellular immune response to any peptide pool was reported. The peptide pools included pre-membrane envelope (prME), capsid (C), non-structural proteins (NS): NS1, NS2, NS3, NS4 and NS5 for DENV-1, DENV-2, DENV-3 and DENV-4.
Measured: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
Magnitude of Cellular Immune Response Assessed by Number of Spot Forming Cells [SFC]/10^6 Peripheral Blood Mononuclear Cells (PBMCs) Measured by IFN-γ ELISpot Responses to TDV
The magnitude of cellular immune response was assessed by the number of SFC/10^6 PBMCs. IFN-γ ELISpot response >3 times higher compared with baseline (no peptide) and ≥5 spots per 10^6 PBMCs was defined as cellular immune response. Cellular immune response to any peptide pool was reported. The peptide pools included prME, C, NS1, NS2, NS3, NS4 and NS5 for DENV-1, DENV-2, DENV-3 and DENV-4.
Measured: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD4+ T Cells by Intracellular Cytokine Staining (ICS)
Phenotype characterization of cellular immune response was performed in a subset of participants with IFN- γ ELISPOT responses >50 SFC/10^6 cells and availability of sufficient cells. Markers included cluster of differentiation (CD) 4, CD8, IFN-γ, tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2). The peptide pools included C, NS1, NS2/4, NS3, NS5 for DENV-2 and prME for DENV-1, DENV-2, DENV-3 and DENV-4.
Measured: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD8+ T Cells by Intracellular Cytokine Staining (ICS)
Phenotype characterization of cellular immune response was performed in a subset of participants with IFN- γ ELISPOT responses >50 SFC/10^6 cells and availability of sufficient cells. Markers included CD4, CD8, IFN-γ, tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2). The peptide pools included C, NS1, NS2/4, NS3, NS5 for DENV-2 and prME for DENV-1, DENV-2, DENV-3 and DENV-4.
Measured: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
Percentage of Participants With Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Percentages were rounded off to the nearest decimal place.
Measured: Days 6, 9, 12, 15, 30 (Month 1), 90 (Month 3), 96, 99, 102, 105, 120 (Month 4)
Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
The duration of vaccine viremia for each vaccine strain was defined as the date when vaccine viremia was last detected (positive result) to date when vaccine viremia was first detected (positive result) + 1 day. It was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral RNA was detected by qRT-PCR assay. Safety Analysis Set included all participants who received at least 1 dose of trial vaccine.
Measured: Up to Day 120 (Month 4)
Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral RNA was detected by qRT-PCR assay.
Measured: Days 6, 9, 12, and 15
Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included injection site 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)], injection site erythema [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)] and injection site swelling [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)]. Only categories for which there was at least 1 participant are reported.
Measured: Within 7 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With Solicited Systemic Reactions Following Each Vaccination
Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and will include fever, headache, asthenia, malaise and myalgia. Severity grades are: 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). A systemic AE of fever (defined as body temperature ≥ 100.4°F regardless of method taken) was derived from a daily temperature reading recorded within 14 days after vaccination. Only categories for which there was at least 1 participant are reported.
Measured: Within 14 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With at Least One Unsolicited Adverse Events (AEs) Following Each Vaccination
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.
Measured: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With Serious Adverse Events (SAEs)
A SAE is defined as any untoward medical occurrence or effect that at any dose 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 aforementioned criteria.
Measured: From first vaccination (Day 1) through end of study (Day 360 [Month 12])
Percentage of Participants With Medically Attended AEs (MAAEs)
MAAEs was defined as AEs leading to a medical visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.
Measured: From first vaccination (Day 1) 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.

28 Dec 20181 Mar 2021

First posted19 Nov 2018
Study start28 Dec 2018
Primary completion1 Mar 2021
Study completion1 Mar 2021

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 (2)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: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03746015
Sponsor's protocol ID: DEN-210
Status last verified: Aug 2025
First submitted: 13 Nov 2018
Last updated: 8 Sep 2025
Results posted: Yes, on ClinicalTrials.gov
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

Mandaric S, Friberg H, Gottardo R, Messer W, Tricou V, Faccin A, Roubinis N, Nadeem I, Gray L, Sharma M, Currier JR, Biswal S. Humoral and cellular responses to a tetravalent dengue vaccine (TAK-003) in adults from a dengue non-endemic region: An open-label phase 2 trial. Vaccine. 2026 Apr 2;77:128373. doi: 10.1016/j.vaccine.2026.128373. Epub 2026 Feb 20.
PubMed 41722532
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

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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A Study to Evaluate V181 Dengue Vaccine in Healthy Participants 2 to 17 Years of Age (V181-005/MOBILIZE-1)
Healthy
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Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection
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Active, not recruiting
A Controlled Human Infection Model of Dengue
Dengue
RecruitingPhase 2/3
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
RecruitingPhase 2
Adaptive Dengue Antiviral Platform Trial
Dengue, Antiviral Drugs

All Dengue Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Phase 2 Trial to Investigate the Humoral and Cell-Mediated Immune Responses and Safety of a Tetravalent Dengue Vaccine Candidate (TDV) Administered Subcutaneously in Flavivirus-Naïve and Dengue-Immune Healthy Adults
ClinicalTrials.gov ID: NCT03746015
Acronym / sponsor ID: DEN-210
Conditions: Dengue Fever
Keywords: Vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 28 Dec 2018 (actual)
Primary completion: 1 Mar 2021 (actual)
Study completion: 1 Mar 2021 (actual)
First posted: 19 Nov 2018 (actual)
Results: Posted 10 Apr 2024

Clinical summary

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

The purpose of this study is to assess the neutralizing antibody response against each dengue serotype post-vaccination.

Detailed description

Group 1: Flavivirus-Naïve Participants Group 2: Dengue-Immune Participants

All participants will receive subcutaneous injection of TDV on Day 1 (Month 0) and Day 90 (Month 3).

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
TDV: Flavivirus-naïve	Experimental	Biological: TDVTetravalent Dengue Vaccine (TDV) 0.5 mL, subcutaneous (SC) injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants who were flavivirus-naïve were included in this group.
TDV: DENV Immune: DENV-1 Positive	Experimental	Biological: TDVTDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by wild type dengue virus serotype-1 (DENV-1) were included in this group.
TDV: DENV Immune: DENV-3 Positive	Experimental	Biological: TDVTDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by DENV-3 were included in this group.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Who are 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.
Group 1 only: immunologically naïve to dengue, Zika, Yellow Fever (YF), Japanese Encephalitis (JE), West Nile (WN) (based on negative results for detection of anti-DENV, anti-Zika, anti-YF, anti-JE, anti-WN antibodies) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days [10 weeks] prior to Day 1 [Month 0]).
Group 2 only: serology consistent with primary infection with either DENV-1 or DENV-3 (defined as detectable neutralizing antibodies against DENV-1 or DENV-3 only, or titers for DENV-1 or DENV-3 ≥4-times higher than titers for the 2 other dengue serotypes) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days [10 weeks] prior to Day 1 [Month 0]).

Key exclusion criteria (13 listed)

Has clinically active significant infection (as assessed by the investigator) or body temperature ≥38°C (100.4°F) within 3 days of the intended date of vaccination.
Has history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
Known or suspected impairment/alteration of immune function including:
Has planned vaccination (during the trial conduct) against any non-dengue flavivirus (eg, Zika, YF, JE, WN, tick-borne encephalitis, or Murray-Valley encephalitis).
Planned travel (during the trial conduct) to any area endemic for dengue.

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
TDVTDV subcutaneous injection comprised of 1 molecularly characterized, attenuated dengue virus strain, and 3 chimeric dengue virus strains with potencies of not less than 3.3, 2.7, 4.0, and 4.5 log10 plaque forming units (PFU) per dose of TDV-1, TDV-2, TDV-3, and TDV-4, respectively.	Biological	TDV: DENV Immune: DENV-1 Positive, TDV: DENV Immune: DENV-3 Positive, TDV: Flavivirus-naïve

Primary outcome

Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15
Time frame: Day 15
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test 50% (MNT50).
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 30 (Month 1)
Time frame: Day 30 (Month 1)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 60 (Month 2)
Time frame: Day 60 (Month 2)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 90 (Month 3)
Time frame: Day 90 (Month 3)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 105
Time frame: Day 105
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 120 (Month 4)
Time frame: Day 120 (Month 4)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 150 (Month 5)
Time frame: Day 150 (Month 5)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 180 (Month 6)
Time frame: Day 180 (Month 6)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 270 (Month 9)
Time frame: Day 270 (Month 9)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.
GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 360 (Month 12)
Time frame: Day 360 (Month 12)
GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

12 secondary outcomes

Percentage of Participants With Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Responses to Tetravalent Dengue Vaccine (TDV)
Time frame: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
Magnitude of Cellular Immune Response Assessed by Number of Spot Forming Cells [SFC]/10^6 Peripheral Blood Mononuclear Cells (PBMCs) Measured by IFN-γ ELISpot Responses to TDV
Time frame: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD4+ T Cells by Intracellular Cytokine Staining (ICS)
Time frame: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD8+ T Cells by Intracellular Cytokine Staining (ICS)
Time frame: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
Percentage of Participants With Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Days 6, 9, 12, 15, 30 (Month 1), 90 (Month 3), 96, 99, 102, 105, 120 (Month 4)
Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Up to Day 120 (Month 4)
Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Days 6, 9, 12, and 15
Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination
Time frame: Within 7 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With Solicited Systemic Reactions Following Each Vaccination
Time frame: Within 14 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With at Least One Unsolicited Adverse Events (AEs) Following Each Vaccination
Time frame: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])
Percentage of Participants With Medically Attended AEs (MAAEs)
Time frame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])

Results and safety

Results posted to the registry on 10 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TDV: Flavivirus-naïve	22	21
TDV: DENV Immune: DENV-1 Positive	4	4
TDV: DENV Immune: DENV-3 Positive	3	3

Primary outcome: Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15

Time frame: Day 15. Geometric mean (95% Confidence Interval). Unit: titer

Measure	TDV: Flavivirus-naïve n = 21	TDV: DENV Immune: DENV-1 Positive n = 2	TDV: DENV Immune: DENV-3 Positive n = 3
DENV-1	58.9 (28.9 to 120.0)	15325.2 (32.4 to 7241076.9)	5510.0 (1271.4 to 23879.4)
DENV-2	11.2 (6.5 to 19.2)	5200.2 (13.9 to 1947484.8)	4142.7 (694.3 to 24718.0)
DENV-3	42.1 (16.2 to 109.8)	2468.7 (0.0 to 272077002.4)	7244.0 (5083.2 to 10323.3)
DENV-4	19.7 (10.6 to 36.7)	1996.4 (0.5 to 8424572.5)	4909.2 (2503.2 to 9628.0)

Population analysed: Per Protocol Set (PPS) included all participants in the Full Analysis Set (FAS) who had no major protocol violations.

Primary outcome: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 30 (Month 1)

Time frame: Day 30 (Month 1). Geometric mean (95% Confidence Interval). Unit: titer

Measure	TDV: Flavivirus-naïve n = 21	TDV: DENV Immune: DENV-1 Positive n = 2	TDV: DENV Immune: DENV-3 Positive n = 3
DENV-1	336.1 (168.8 to 669.3)	45437.3 (58.0 to 35607948.4)	11091.9 (706.7 to 174081.3)
DENV-2	11557.1 (6408.8 to 20841.2)	12317.0 (2677.3 to 56665.6)	12221.9 (1004.9 to 148651.5)
DENV-3	344.7 (146.3 to 812.6)	7273.6 (2983.8 to 17730.9)	19062.2 (3584.4 to 101373.6)
DENV-4	141.1 (69.1 to 288.0)	5094.3 (888.2 to 29218.2)	5231.1 (2064.2 to 13256.7)

Population analysed: PPS included all participants in the FAS who had no major protocol violations.

Primary outcome: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 60 (Month 2)

Time frame: Day 60 (Month 2). Geometric mean (95% Confidence Interval). Unit: titer

Measure	TDV: Flavivirus-naïve n = 21	TDV: DENV Immune: DENV-1 Positive n = 2	TDV: DENV Immune: DENV-3 Positive n = 3
DENV-1	258.5 (102.0 to 655.4)	28109.0 (65.7 to 12030804.9)	7827.8 (1701.7 to 36007.3)
DENV-2	6293.0 (3655.7 to 10833.1)	9641.1 (4219.1 to 22030.9)	7236.5 (432.9 to 120961.1)
DENV-3	174.6 (79.7 to 382.9)	6174.2 (200.8 to 189874.6)	15536.5 (3282.7 to 73532.6)
DENV-4	78.2 (35.0 to 174.7)	6122.7 (1974.7 to 18984.1)	4254.8 (720.8 to 25116.0)

Population analysed: PPS included all participants in the FAS who had no major protocol violations.

Primary outcome: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 90 (Month 3)

Time frame: Day 90 (Month 3). Geometric mean (95% Confidence Interval). Unit: titer

Measure	TDV: Flavivirus-naïve n = 21	TDV: DENV Immune: DENV-1 Positive n = 2	TDV: DENV Immune: DENV-3 Positive n = 3
DENV-1	197.5 (82.7 to 471.7)	24989.5 (244.4 to 2554755.6)	8111.3 (2866.7 to 22950.5)
DENV-2	4077.0 (2535.6 to 6555.5)	9167.4 (4646.6 to 18086.6)	5450.5 (857.1 to 34661.2)
DENV-3	145.7 (82.0 to 258.9)	7043.3 (1348.3 to 36792.6)	10172.1 (3690.3 to 28038.7)
DENV-4	79.2 (37.3 to 168.0)	3240.2 (9.6 to 1095309.8)	4372.2 (857.1 to 22304.5)

Population analysed: PPS included all participants in the FAS who had no major protocol violations.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality and Serious Adverse Events: From first vaccination through end of study (Day 360 [Month 12]); Non-serious (Other) AEs: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Day 1 [Month 0] and Day 90 [Month 3]. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TDV: Flavivirus-naïve	1 of 22 (4.5%)	22 of 22 (100%)	0 of 22
TDV: DENV Immune: DENV-1 Positive	1 of 4 (25%)	4 of 4 (100%)	0 of 4
TDV: DENV Immune: DENV-3 Positive	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Unassigned Group	0 of 1 (0%)	0 of 1 (0%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41722532Mandaric S, Friberg H, Gottardo R, Messer W, Tricou V, Faccin A, Roubinis N, Nadeem I, Gray L, Sharma M, Currier JR, Biswal S. Humoral and cellular responses to a tetravalent dengue vaccine (TAK-003) in adults from a dengue non-endemic region: An open-label phase 2 trial. Vaccine. 2026 Apr 2;77:128373. doi: 10.1016/j.vaccine.2026.128373. Epub 2026 Feb 20.
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.
Individual participant dataSharing planned: 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.

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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.

Medical Director study director

Takeda

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TDV in people with Dengue Fever, run by Takeda at 2 sites in United States.

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 3 inclusion and 13 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 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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 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 10 Apr 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 (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15 (time frame: Day 15). The study lists 10 primary outcomes in all. 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 NCT03746015, which also lists 2 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 8 Sep 2025.