Dengue FeverPhase 2NCT02425098

Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in Singapore

A Phase 2 study testing Takeda's Tetravalent Dengue Vaccine Candidate (TDV) and Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV) in people with Dengue Fever, run by Takeda at 3 sites in Singapore.

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 post-vaccination neutralizing antibody response against each dengue serotype by vaccine group. Read more about this study

Who is it for?: Ages 21 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever
What is being tested?: Takeda's Tetravalent Dengue Vaccine Candidate (TDV) and Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 351 participants
Where: 3 sitesSingapore
Study dates: 3 Jun 2015to 18 Sep 2017
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 21 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Participant signs and dates a written informed consent form where applicable, 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.
Is aged 21 to 45 years of age, inclusive.
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.
Can comply with trial procedures and are available for the duration of follow-up.
Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.

Who cannot join

Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
Has history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial, including but not limited to:
Known hypersensitivity or allergy to any of the vaccine components.
Female participants who are pregnant or breastfeeding.
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).
Known or suspected impairment/alteration of immune function, including:

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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 (Month 0) (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 (Month 0).
iii. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
iv. Receipt of immunostimulants within 60 days prior to Day 1(Month 0).
v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
vi. Human immunodeficiency virus (HIV) infection and HIV-related diseases.
vii. Hepatitis C virus (HCV) infection.
viii. Genetic immunodeficiency.
Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
Is first-degree relative of individuals involved in trial conduct.
For females 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 (Month 0).
Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
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 Day 1 [Month 0]).
Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method from signing the informed consent up to 6 weeks post-vaccination.

Trial locations and contacts

3 sites in 1 country.

Singapore3 sites

Singapore General Hospital
Singapore, 169608
Tan Tock Seng Hospital
Singapore, 308433
Changi General Hospital
Singapore, 529889

Other trials in Singapore

About this study

Official title: A Phase II, Double-Blind, Randomized, Controlled Trial to Assess the Safety and Immunogenicity of a Tetravalent Dengue Vaccine With Two Different Serotype 2 Potencies in an Adult Population in Singapore

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

Read the detailed description

The vaccine being tested in this study was Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study looked at safety and the titers of antibodies to dengue fever induced in people who were administered a high-dose of TDV (HD-TDV) compared to TDV.

The study enrolled 351 patients. Before being assigned to a treatment group participants were screened for previous exposure to the dengue virus using a Dengue immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Participants were randomly assigned in 1:1 ratio (by chance) to one of the two treatment groups-which remained undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

HD-TDV 0.5 mL subcutaneous injection
TDV 0.5 mL subcutaneous injection

All participants received a single injection on Day 1. Participants were asked to record any symptoms that may or may not be related to the vaccine or the injection site in a diary card for 28 days after vaccination.

This multi-center trial was conducted in Singapore. The overall time of participation in this study was 12 months. Participants made multiple visits to the clinic, including a final visit 1 year after receiving their dose of TDV.

Conditions: Dengue Fever
Being tested: Takeda's Tetravalent Dengue Vaccine Candidate (TDV), Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-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.

Takeda's Tetravalent Dengue Vaccine Candidate (TDV)Biological
TDV subcutaneous injection
Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)Biological
High-dose TDV subcutaneous injection

Study groups in NCT02425098
Study group	Role	What they receive
High-dose Tetravalent Dengue Vaccine (HD-TDV)	Experimental	High-dose Tetravalent Dengue Vaccine [HD-TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 210^4 plaque forming units (PFU), 510^4 PFU, 110^5 PFU, and 310^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively. Receives: Biological: Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)
Tetravalent Dengue Vaccine (TDV)	Experimental	Tetravalent Dengue Vaccine [TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 210^4 plaque forming units (PFU), 510^3 PFU, 110^5 PFU, and 310^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively. Receives: Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

What is being measured

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

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test [MNT].
Measured: Day 15
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Measured: Day 30
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Measured: Day 90
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Measured: Day 180
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Measured: Day 365
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Day 15
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Day 30
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Day 90
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Day 180
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Day 365

Secondary outcomes (9)

Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], erythema [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)] and swelling [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)].
Measured: Within 7 days after Vaccination
Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). A systemic AE of fever (defined as ≥ 100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination.
Measured: Within 14 days after Vaccination
Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.
Measured: Within 28 days after Vaccination
Number of Participants With Serious Adverse Events (SAEs)
A serious adverse event (SAE) is 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 above-mentioned criteria.
Measured: From first vaccination through end of study (Day 365)
Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
Baseline dengue seropositivity was based on the microneutralization test (MNT) result and was defined as a reciprocal neutralizing titer ≥10 for one or more dengue serotype at baseline. The four DENV serotypes are DENV-1, DENV-2, DENV-3, and DENV-4.
Measured: Days 15, 30, 90, 180 and 365
Seropositivity Rate for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
Baseline dengue seropositivity was based on the MNT result and was defined as a reciprocal neutralizing titer ≥10 for one or more dengue serotype at baseline. Seropositive rate was defined as a reciprocal neutralizing titer ≥ 10. Seropositivity was assessed for the four Dengue serotypes are DENV-1, DENV-2, DENV-3, and DEN-4.
Measured: Days 15, 30, 90, 180, and 365
Percentage of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Vaccine Viremia was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.
Measured: Days 5, 7, 9, 11, 15, 17, 21 and 30
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 ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.
Measured: Days 5, 7, 9, 11, 15, 17, 21 and 30
Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Vaccine Viremia was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.
Measured: Days 5, 7, 9, 11, 15, 17, 21 and 30

Timeline

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

3 Jun 201518 Sep 2017

First posted23 Apr 2015 (estimated)
Study start3 Jun 2015
Primary completion18 Sep 2017
Study completion18 Sep 2017

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 (4)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: 351 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02425098
Sponsor's protocol ID: DEN-205
Other IDs: U1111-1166-8884
Status last verified: Jul 2019
First submitted: 9 Apr 2015
Last updated: 28 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

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
White LJ, Young EF, Stoops MJ, Henein SR, Adams EC, Baric RS, de Silva AM. Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003). PLoS Negl Trop Dis. 2021 Mar 12;15(3):e0009258. doi: 10.1371/journal.pntd.0009258. eCollection 2021 Mar.
PubMed 33711074
Michlmayr D, Andrade P, Nascimento EJM, Parker A, Narvekar P, Dean HJ, Harris E. Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine. J Infect Dis. 2021 Feb 3;223(2):247-257. doi: 10.1093/infdis/jiaa346.
PubMed 32572472
Tricou V, Low JG, Oh HM, Leo YS, Kalimuddin S, Wijaya L, Pang J, Ling LM, Lee TH, Brose M, Hutagalung Y, Rauscher M, Borkowski A, Wallace D. Safety and immunogenicity of a single dose of a tetravalent dengue vaccine with two different serotype-2 potencies in adults in Singapore: A phase 2, double-blind, randomised, controlled trial. Vaccine. 2020 Feb 5;38(6):1513-1519. doi: 10.1016/j.vaccine.2019.11.061. Epub 2019 Dec 13.
PubMed 31843269

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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Dengue
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Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
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Adaptive Dengue Antiviral Platform Trial
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All Dengue Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Double-Blind, Randomized, Controlled Trial to Assess the Safety and Immunogenicity of a Tetravalent Dengue Vaccine With Two Different Serotype 2 Potencies in an Adult Population in Singapore
ClinicalTrials.gov ID: NCT02425098
Acronym / sponsor ID: DEN-205
Conditions: Dengue Fever
Keywords: Vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 351 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 3 Jun 2015 (actual)
Primary completion: 18 Sep 2017 (actual)
Study completion: 18 Sep 2017 (actual)
First posted: 23 Apr 2015 (estimated)
Results: Posted 28 Aug 2019

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 post-vaccination neutralizing antibody response against each dengue serotype by vaccine group.

Detailed description

HD-TDV 0.5 mL subcutaneous injection
TDV 0.5 mL subcutaneous injection

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
High-dose Tetravalent Dengue Vaccine (HD-TDV)	Experimental	Biological: Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)High-dose Tetravalent Dengue Vaccine [HD-TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 210^4 plaque forming units (PFU), 510^4 PFU, 110^5 PFU, and 310^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.
Tetravalent Dengue Vaccine (TDV)	Experimental	Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)Tetravalent Dengue Vaccine [TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 210^4 plaque forming units (PFU), 510^3 PFU, 110^5 PFU, and 310^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.

Who may qualify

Ages: 21 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Participant signs and dates a written informed consent form where applicable, 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.
Is aged 21 to 45 years of age, inclusive.
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.
Can comply with trial procedures and are available for the duration of follow-up.
Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.

Key exclusion criteria (26 listed)

Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
Has history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial, including but not limited to:
Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.

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	Tetravalent Dengue Vaccine (TDV)
Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)High-dose TDV subcutaneous injection	Biological	High-dose Tetravalent Dengue Vaccine (HD-TDV)

Primary outcome

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15
Time frame: Day 15
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test [MNT].
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30
Time frame: Day 30
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90
Time frame: Day 90
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
Time frame: Day 180
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365
Time frame: Day 365
GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15
Time frame: Day 15
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30
Time frame: Day 30
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90
Time frame: Day 90
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180
Time frame: Day 180
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.
Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365
Time frame: Day 365
Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

9 secondary outcomes

Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Time frame: Within 7 days after Vaccination
Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Time frame: Within 14 days after Vaccination
Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination
Time frame: Within 28 days after Vaccination
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From first vaccination through end of study (Day 365)
Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
Time frame: Days 15, 30, 90, 180 and 365
Seropositivity Rate for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status
Time frame: Days 15, 30, 90, 180, and 365
Percentage of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Days 5, 7, 9, 11, 15, 17, 21 and 30
Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Days 5, 7, 9, 11, 15, 17, 21 and 30
Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
Time frame: Days 5, 7, 9, 11, 15, 17, 21 and 30

Results and safety

Results posted to the registry on 28 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
High-dose Tetravalent Dengue Vaccine (HD-TDV)	176	163
Tetravalent Dengue Vaccine (TDV)	175	159

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

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

Measure	High-dose Tetravalent Dengue Vaccine (HD-TDV) n = 173	Tetravalent Dengue Vaccine (TDV) n = 174
DENV-1	156.2 (98.0 to 249.1)	110.2 (73.8 to 164.6)
DENV-2	183.0 (116.7 to 287.0)	117.6 (75.8 to 182.4)
DENV-3	113.5 (74.7 to 172.6)	69.0 (47.1 to 100.9)
DENV-4	41.2 (29.7 to 57.2)	33.9 (25.3 to 45.4)

Population analysed: Per-protocol set (PPS) included all randomized participants who received study vaccine and for whom valid pre-dosing and at least one valid post-dosing MNT result was available, and who had no major protocol violations. Here 'number analyzed' refers to participants with valid MNT results available at given time-point.

Primary outcome: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30

Time frame: Day 30. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	High-dose Tetravalent Dengue Vaccine (HD-TDV) n = 173	Tetravalent Dengue Vaccine (TDV) n = 174
DENV-1	771.0 (525.1 to 1132.0)	470.5 (324.4 to 682.4)
DENV-2	8640.3 (7157.0 to 10431.0)	1992.7 (1334.5 to 2975.5)
DENV-3	390.6 (262.1 to 582.2)	250.8 (168.9 to 372.5)
DENV-4	110.2 (78.3 to 155.2)	143.3 (107.0 to 191.8)

Population analysed: The PPS included all randomized participants who received the study vaccine and for whom valid pre-dosing and at least one valid post-dosing MNT result was available, and who had no major protocol violations. Here 'number analyzed' refers to participants with valid MNT results available at given time-point.

Primary outcome: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90

Time frame: Day 90. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	High-dose Tetravalent Dengue Vaccine (HD-TDV) n = 173	Tetravalent Dengue Vaccine (TDV) n = 174
DENV-1	376.5 (246.8 to 574.3)	394.0 (265.0 to 585.9)
DENV-2	4090.2 (3439.8 to 4863.6)	1647.3 (1158.5 to 2342.4)
DENV-3	266.5 (177.6 to 399.9)	218.0 (148.1 to 320.8)
DENV-4	85.6 (61.7 to 118.6)	117.4 (87.2 to 158.1)

Primary outcome: Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180

Time frame: Day 180. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	High-dose Tetravalent Dengue Vaccine (HD-TDV) n = 173	Tetravalent Dengue Vaccine (TDV) n = 174
DENV-1	379.4 (252.3 to 570.3)	312.2 (212.2 to 459.2)
DENV-2	2585.5 (2088.8 to 3200.3)	1235.0 (890.7 to 1712.5)
DENV-3	236.2 (162.2 to 344.0)	161.0 (110.5 to 234.6)
DENV-4	91.0 (65.7 to 125.9)	92.9 (68.9 to 125.4)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Unsolicited AEs: Within 28 days after Vaccination; SAEs: From first vaccination through end of study (Day 365). Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
High-dose Tetravalent Dengue Vaccine (HD-TDV)	3 of 176 (1.7%)	45 of 176 (25.6%)	0 of 176
Tetravalent Dengue Vaccine (TDV)	3 of 175 (1.7%)	49 of 175 (28%)	0 of 175

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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 33711074White LJ, Young EF, Stoops MJ, Henein SR, Adams EC, Baric RS, de Silva AM. Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003). PLoS Negl Trop Dis. 2021 Mar 12;15(3):e0009258. doi: 10.1371/journal.pntd.0009258. eCollection 2021 Mar.
Derived from this study: PubMed 32572472Michlmayr D, Andrade P, Nascimento EJM, Parker A, Narvekar P, Dean HJ, Harris E. Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine. J Infect Dis. 2021 Feb 3;223(2):247-257. doi: 10.1093/infdis/jiaa346.
Derived from this study: PubMed 31843269Tricou V, Low JG, Oh HM, Leo YS, Kalimuddin S, Wijaya L, Pang J, Ling LM, Lee TH, Brose M, Hutagalung Y, Rauscher M, Borkowski A, Wallace D. Safety and immunogenicity of a single dose of a tetravalent dengue vaccine with two different serotype-2 potencies in adults in Singapore: A phase 2, double-blind, randomised, controlled trial. Vaccine. 2020 Feb 5;38(6):1513-1519. doi: 10.1016/j.vaccine.2019.11.061. Epub 2019 Dec 13.

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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 Clinical Science study director

Takeda

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

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 26 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 28 Aug 2019. 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 Singapore. 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 28 Aug 2019). 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 Neutralizing Antibody Titer (GMT) 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 NCT02425098, which also lists 4 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 28 Aug 2019.