Last reviewed · How we verify

NCT03771963

Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) at the End of Shelf Life in Healthy Adults

Completed Phase 3 Results posted Last updated 7 June 2021
What this trial tests

Phase 3 trial testing Tetravalent Dengue Vaccine (TDV) in Dengue Fever in 200 participants. Completed in 13 March 2020.

Timeline
28 March 2019
Primary endpoint
14 October 2019
13 March 2020

Quick facts

Lead sponsorTakeda
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeprevention
Enrollment200
Start date28 March 2019
Primary completion14 October 2019
Estimated completion13 March 2020
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 60, any sex, with Dengue Fever. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 Primary · One month post second dose (Day 120)

GMTs of neutralizing antibodies for each of the 4 dengue serotypes were measured by microneutralization test 50% \[MNT50\]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3, and DENV-4.

DENV-1
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)557.4417.0 – 744.9
DENV-2
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)2047.41739.7 – 2409.5
DENV-3
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)131.8105.0 – 165.4
DENV-4
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)119.697.7 – 146.5
Seropositivity Rates for Each of the 4 Dengue Serotypes at Days 120 and 270 Secondary · One month and six months post second dose (Days 120 and 270)

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.

Day 120: DENV-1
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)99.295.9 – 100.0
Day 120: DENV-2
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)100.097.2 – 100.0
Day 120: DENV-3
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)97.793.5 – 99.5
Day 120: DENV-4
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)99.295.9 – 100.0
Day 270: DENV-1
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)97.092.5 – 99.2
Day 270: DENV-2
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)98.594.7 – 99.8
Day 270: DENV-3
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)85.778.6 – 91.2
Day 270: DENV-4
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)86.579.5 – 91.8
Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at Days 120 and 270 Secondary · One month and six months post second dose (Days 120 and 270)

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. The dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity for multiple dengue serotypes was summarized in the following categories: tetravalent and at least trivalent.

Day 120: At Least Trivalent
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)99.295.9 – 100.0
Day 120: Tetravalent
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)97.092.4 – 99.2
Day 270: At Least Trivalent
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)91.084.8 – 95.3
Day 270: Tetravalent
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)78.971.0 – 85.5
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 Secondary · Six months post second dose (Day 270)

GMTs of neutralizing antibodies were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

DENV-1
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)311.6222.8 – 435.9
DENV-2
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)1170.6953.9 – 1436.5
DENV-3
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)63.048.4 – 82.0
DENV-4
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)57.644.2 – 75.0
Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity Secondary · Up to 7 days (Day of vaccination + 6 subsequent days) after each of the vaccination

Solicited local adverse events (AEs) \[at injection site\] were collected by participants using diary cards within 7 days after each 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 \[Grade 0 (\<25 mm), 1 (25 - ≤ 50 mm), 2 (\>50 - ≤ 100 mm), 3 (\> 100 mm)\]. The per

After First Vaccination, Any Solicited Local AEs
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)35.9
After First Vaccination, Pain: Any Severity
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)29.7
After First Vaccination, Pain: Mild
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)25.5
After First Vaccination, Pain: Moderate
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)3.6
After First Vaccination, Pain: Severe
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)0.5
After First Vaccination, Erythema: Any Severity
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)13.0
After First Vaccination, Erythema: Mild
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)12.0
After First Vaccination, Erythema: Moderate
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)1.0
Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity Secondary · Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination

Solicited systemic AEs were collected by participants using diary cards within 14 days after each vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). Fever is defined as body temperature greater than or equal to 38°C (100.4°F). Fever was excluded from the overall count as no severity grading was applied for it. The percentages were

After First Vaccination, Any Solicited Systemic Local AEs
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)42.2
After First Vaccination, Headache: Any Severity
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)30.2
After First Vaccination, Headache: Mild
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)22.9
After First Vaccination, Headache: Moderate
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)5.7
After First Vaccination, Headache: Severe
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)1.6
After First Vaccination, Myalgia: Any Severity
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)25.5
After First Vaccination, Myalgia: Mild
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)20.8
After First Vaccination, Myalgia: Moderate
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)3.1
Percentage of Participants With Any Unsolicited Adverse Events Following Each Vaccination Secondary · Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days)

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.

After First Vaccination
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)11.5
After Second Vaccination
GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)10.8
Percentage of Participants With Serious Adverse Events (SAEs) Secondary · From first vaccination (Day 1) through end of study (Day 270)

An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, leads to a congenital anomaly / birth defect in the offspring of a participant, or is an important medical event which may require intervention to prevent the items listed above or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)2.5
Percentage of Participants With Medically Attended Adverse Events (MAAEs) Secondary · From first vaccination (Day 1) through end of study (Day 270)

MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.

GroupValue95% CI
Tetravalent Dengue Vaccine (TDV)26.0

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality and Serious adverse events: From first vaccination (Day 1) through end of study (Day 270). Other (Non-serious) adverse events: Up to 28 days after each vaccination (Day of vaccination + 27 subsequent days).. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tetravalent Dengue Vaccine (TDV)
Serious: 5/200 (3%)
Deaths: 0/200

Serious adverse events (5 terms)

ReactionSystemTetravalent Dengue Vaccine…
BradycardiaCardiac disorders
Inguinal herniaGastrointestinal disorders
Hepatic failureHepatobiliary disorders
SepsisInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Bradycardia, Inguinal hernia, Hepatic failure, Sepsis, Osteoarthritis.

Data from ClinicalTrials.gov NCT03771963 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety and immune response of a naturally aged lot of tetravalent dengue vaccine (TDV) in healthy participants, aged 18 to 60 years, in non-endemic country(ies) for dengue.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. An open-label, Phase 3 trial of TAK-003, a live attenuated dengue tetravalent vaccine, in healthy US adults: immunogenicity and safety when administered during the second half of a 24-month shelf-life.
    Patel SS, Winkle P, Faccin A, Nordio F, et al · · 2023 · cited 25× · PMID 37846724 · DOI 10.1080/21645515.2023.2254964
  2. Immunogenicity, Safety and Efficacy of the Dengue Vaccine TAK-003: A Meta-Analysis.
    Flacco ME, Bianconi A, Cioni G, Cioni G, et al · · 2024 · cited 13× · PMID 39066408 · DOI 10.3390/vaccines12070770
  3. Opportunities and challenges of mRNA technologies in development of dengue virus vaccine.
    Liu X. · · 2025 · cited 9× · PMID 40109333 · DOI 10.3389/fimmu.2025.1520968
  4. Pathogenesis and clinical management of arboviral diseases.
    Cenci Dietrich V, Costa JMC, Oliveira MMGL, Aguiar CEO, et al · · 2025 · cited 6× · PMID 40134841 · DOI 10.5501/wjv.v14.i1.100489
  5. Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine.
    Rauscher M, Youard Z, Faccin A, Patel SS, et al · · 2025 · cited 2× · PMID 40099800 · DOI 10.1080/14760584.2025.2480297

Verify or expand the search:

Other trials of Tetravalent Dengue Vaccine (TDV)

Trials testing the same drug.

Other recruiting trials for Dengue Fever

Currently open trials in the same condition.

Other Takeda trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03771963.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing