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Dengue FeverPhase 3NCT03771963

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

A Phase 3 study testing Tetravalent Dengue Vaccine (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.

Official record
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Trial summary

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. 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?
Tetravalent Dengue Vaccine (TDV)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
2 sitesUnited States
Study dates
28 Mar 2019to 13 Mar 2020
Phase
Phase 3
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

  • Participants who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs), and the clinical judgment of the investigator.
  • Participants who sign and date a written informed consent form 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.

Who cannot join

  • Participants with a clinically significant active infection (as assessed by the investigator) or body temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccine administration
  • 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 the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
  • Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
Show all 18Show fewer
  • 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.
  • With Body Mass Index (BMI) greater than or equal to 35 kg/m^2(=weight in kg/height in meters^2).
  • Participants who have known hypersensitivity or allergy to any of the vaccine components.
  • Previous and planned vaccination (during the trial conduct), against any flavivirus including dengue, Yellow Fever (YF), Japanese Encephalitis (JE) viruses or tick-borne encephalitis.
  • Previous participation in any clinical trial of a dengue or other flavivirus (e.g., West Nile [WN] virus) candidate vaccine, except for participants who received placebo in those trials.
  • With a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.
  • Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
  • Participants with history of substance or alcohol abuse within the past 2 years.
  • Participants who have any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Anaheim Clinical Trials, LLC

    Anaheim, California, 92805

  • Hutchinson Clinic

    Hutchinson, Kansas, 67502

Other trials in United States

About this study

Official title: An Open-Label, Phase 3 Trial to Investigate the Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) at the End of Shelf Life in Healthy Adults in Non-Endemic Country(Ies) for Dengue

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.

Read the detailed description

The vaccine being tested in this study is tetravalent dengue vaccine (TDV). The primary objective of this study is to evaluate the immune response and safety of a naturally aged (>12 months stored at 2°C to 8°C) lot of TDV in a healthy adult population in country(ies) non-endemic for dengue. The assessment of a naturally aged lot of TDV in this clinical trial will provide an important contribution to data on TDV stability throughout the shelf life of the product.

The study will enroll approximately 200 participants. Participants will be enrolled to the one treatment group:

Tetravalent Dengue Vaccine (TDV)

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

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 9 months. Participants will make multiple visits to the clinic including a final visit at Day 270 (Month 9).

Conditions
Dengue Fever
Being tested
Tetravalent Dengue Vaccine (TDV)
Keywords
Live Attenuated Tetravalent Dengue Vaccine
Medical subject headings
Dengue

What participants receive

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

  • Tetravalent Dengue Vaccine (TDV)Biological

    TDV SC injection.

Study groups in NCT03771963
Study groupRoleWhat they receive
Tetravalent Dengue Vaccine (TDV)ExperimentalTDV 0.5 mL, injection, subcutaneously (SC), once on Day 1 (first dose) and Day 90 (second dose).
Receives: Biological: Tetravalent Dengue Vaccine (TDV)

What is being measured

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

  1. Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 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.

    Measured: One month post second dose (Day 120)

Secondary outcomes (8)
  1. Seropositivity Rates for Each of the 4 Dengue Serotypes at 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.

    Measured: One month and six months post second dose (Days 120 and 270)

  2. Seropositivity Rates for Multiple (2, 3, or 4) Dengue Serotypes at 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.

    Measured: One month and six months post second dose (Days 120 and 270)

  3. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270

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

    Measured: Six months post second dose (Day 270)

  4. Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination by Severity

    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 percentages were rounded off to the first decimal place. Only categories with at least 1 participant are reported.

    Measured: Up to 7 days (Day of vaccination + 6 subsequent days) after each of the vaccination

  5. Percentage of Participants With Solicited Systemic Adverse Events Following Each Vaccination by Severity

    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 rounded off to the first decimal place. Only categories with at least 1 participant are reported.

    Measured: Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination

  6. Percentage of Participants With Any Unsolicited Adverse Events 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 after each vaccination (Day of vaccination + 27 subsequent days)

  7. Percentage of Participants With Serious Adverse Events (SAEs)

    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.

    Measured: From first vaccination (Day 1) through end of study (Day 270)

  8. Percentage of Participants With Medically Attended Adverse Events (MAAEs)

    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.

    Measured: From first vaccination (Day 1) through end of study (Day 270)

Timeline

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

  1. First posted11 Dec 2018
  2. Study start28 Mar 2019
  3. Primary completion14 Oct 2019
  4. Study completion13 Mar 2020

Resources

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 3
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03771963
Sponsor's protocol ID
DEN-307
Other IDs
U1111-1222-2812
Status last verified
May 2021
First submitted
10 Dec 2018
Last updated
7 Jun 2021
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

  • 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
  • Patel SS, Winkle P, Faccin A, Nordio F, LeFevre I, Tsoukas CG. 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. Hum Vaccin Immunother. 2023 Aug;19(2):2254964. doi: 10.1080/21645515.2023.2254964. Epub 2023 Oct 17.

    PubMed 37846724

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tetravalent Dengue Vaccine (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 2 inclusion and 18 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 7 Jun 2021. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 7 Jun 2021). 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 4 Dengue Serotypes at Day 120 (time frame: One month post second dose (Day 120)). 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 NCT03771963, 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 7 Jun 2021.

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