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DenguePhase 3NCT03341637

Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) in Adolescents in Non-Endemic Area(s)

A Phase 3 study testing Tetravalent Dengue Vaccine (TDV) in people with Dengue, run by Takeda at 5 sites in Mexico.

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 was to describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent participants. Read more about this study

Who is it for?
Ages 12 to 17 yearsHealthy volunteers can take part
Conditions the study is for
Dengue
What is being tested?
Tetravalent Dengue Vaccine (TDV)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
400 participants
Where
5 sitesMexico
Study dates
14 Dec 2017to 26 Jan 2019
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 12 to 17 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • The participant is aged 12 to 17 years, inclusive;
  • Is 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.
  • The participant/the participant's legally authorized representative (LAR) signs and dates a written, informed consent/assent 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.
  • Individuals who can comply with trial procedures and are available for the duration of follow-up.

Who cannot join

  • Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
  • Known hypersensitivity or allergy to any of the vaccine components.
  • Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the participant's ability to participate in the trial.
  • Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barre syndrome).
  • History or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose additional risk to the participant due to participation in the trial.
  • Has known or suspected impairment/alteration of immune function, including:
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  • 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 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
  • 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 (M0).
  • Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
  • Receipt of immune-stimulants within 60 days prior to Day 1 (M0).
  • Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
  • Human immunodeficiency virus (HIV) infection or HIV-related disease.
  • Genetic immunodeficiency.
  • Has abnormalities of splenic or thymic function.
  • Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding.
  • Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
  • Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg/[height in square meters]).
  • Individuals participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intent to participate in another clinical trial at any time during the conduct of this trial.
  • Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of trial vaccine administration.
  • Individuals involved in the trial conduct or their first degree relatives.
  • Has history of substance or alcohol abuse within the past 2 years.
  • Female participants who are pregnant or breastfeeding.
  • 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 (M0).
  • Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks after the last dose of trial vaccine. In addition, they must be advised not to donate ova during this period.
  • Any positive or indeterminate pregnancy test.
  • Previous and planned vaccination (during the trial conduct), against any flaviviruses 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 (eg, West Nile [WN] virus) candidate vaccine, except for participants who received placebo in those trials.
  • Participants with documented or suspected disease caused by a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Mexico5 sites
  • Instituto Nacional de Pediatria (INP)

    Mexico City, 04530

  • Hospital Infantil de Mexico Federico Gomez

    Mexico City, 06720

  • Biodextra, S.A. de C.V.

    Mexico City, 09360

  • Mexico Centre for Clinical Research

    Mexico City, ZC 03100

  • Centro de Atencion E Investigacion Medica (CAIMED) Mexico DF

    Mexico City

Other trials in Mexico

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Immunogenicity and Safety of Subcutaneous Administration of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescent Subjects in Non-Endemic Area(s) for Dengue

The purpose of this study was to describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent participants.

Read the detailed description

The vaccine tested in this study was tetravalent dengue vaccine (TDV). TDV was tested to assess the safety and immunogenicity in healthy adolescents in non-endemic area(s) for dengue.

The study enrolled 400 healthy participants. Participants were randomized in 3:1 ratio to receive:

  • TDV 0.5 mL subcutaneous injection
  • Placebo normal saline solution (0.9% NaCl) for injection.

In each trial group, participants received 2-dose schedule of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3), but not all participants received both doses (8 subjects discontinued the trial before receiving the second dose).

This multi-center trial was conducted in Mexico. The overall time to participate in this study was 270 days. Participants had multiple visits to the clinic including a final visit at Day 270.

Conditions
Dengue
Being tested
Tetravalent Dengue Vaccine (TDV), Placebo
Keywords
Drug Therapy
Medical subject headings
Dengue

What participants receive

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

  • Tetravalent Dengue Vaccine (TDV)Biological

    TDV subcutaneous injection

  • PlaceboBiological

    Normal Saline (0.9% NaCl) subcutaneous injection

Study groups in NCT03341637
Study groupRoleWhat they receive
Tetravalent Dengue Vaccine (TDV)ExperimentalTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose)
Receives: Biological: Tetravalent Dengue Vaccine (TDV)
PlaceboPlacebo comparatorTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).
Receives: Biological: Placebo

What is being measured

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

  1. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120

    GMTs of neutralizing antibodies were measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity is defined as reciprocal neutralizing titer ≥10.

    Measured: One month post second dose (Day 120)

Secondary outcomes (8)
  1. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270

    GMTs of neutralizing antibodies were measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Seropositivity is defined as reciprocal neutralizing titer ≥10.

    Measured: Six months post second dose (Day 270)

  2. Seropositivity Rates for Each of the 4 Dengue Serotypes

    Seropositivity rate, defined as the percentage of participants seropositive, was derived from the titers of dengue-neutralizing antibodies. Seropositivity defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

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

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

    Seropositivity rate, defined as the percentage of participants seropositive, was derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10.

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

  4. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Each Vaccination by Severity

    Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (<2.5 cm, mild: 2.5-5 cm, moderate: >5 to <=10 cm, severe: >10 cm) and swelling (edema/induration) (<2.5 cm, mild: 2.5-5 cm, moderate: >5 to <=10 cm, severe: >10 cm).

    Measured: Within 7 days after each vaccination

  5. Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Each Vaccination by Severity

    Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and included fever, headache, tiredness or weakness (asthenia), feeling of discomfort (malaise) and muscle pain (myalgia). Severity scales for headache were none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents normal activity with or without treatment. Severity scales for others were none, mild: no interference with daily activity, moderate: interference with daily activity and severe: prevents daily activity. A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it.

    Measured: Within 14 days after each vaccination

  6. Percentage of Participants With Any Unsolicited Adverse Events (AEs) Following Each Vaccination

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.

    Measured: Within 28 days after each vaccination

  7. Percentage of Participants With Medically Attended AEs (MAAEs) Throughout the Study

    MAAEs were 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 270)

  8. Percentage of Participants With Serious Adverse Events (SAEs) Throughout the Study

    An SAE was defined as any untoward medical occurrence or effect that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.

    Measured: From first vaccination (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 posted14 Nov 2017
  2. Study start14 Dec 2017
  3. Primary completion26 Jan 2019
  4. Study completion26 Jan 2019

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
400 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03341637
Sponsor's protocol ID
DEN-315
Other IDs
U1111-1192-7827, RNEC-2017-DEN-315, 2018-003980-77, 2018
Status last verified
Jul 2019
First submitted
9 Nov 2017
Last updated
15 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

  • 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
  • Biswal S, Mendez Galvan JF, Macias Parra M, Galan-Herrera JF, Carrascal Rodriguez MB, Rodriguez Bueno EP, Brose M, Rauscher M, LeFevre I, Wallace D, Borkowski A. Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naive adolescents in Mexico City. Rev Panam Salud Publica. 2021 Jun 11;45:e67. doi: 10.26633/RPSP.2021.67. eCollection 2021.

    PubMed 34131423

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tetravalent Dengue Vaccine (TDV) in people with Dengue, run by Takeda at 5 sites in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 28 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 15 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 5 sites in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 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 15 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 Titers (GMTs) 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 NCT03341637, 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 15 Aug 2019.

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