Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose

NCT ID: NCT03999996

Last Updated: 2025-06-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

365 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-12

Study Completion Date

2024-05-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to describe antibody persistence for each of the 4 dengue serotypes for up to 63 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-315 (NCT03341637) (Mexico) and for up to 36 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-304 (NCT03423173) (United States \[US\]) and to describe the impact of a tetravalent dengue vaccine (TDV) booster dose vs placebo on antibody response for each of the 4 dengue serotypes at 1 month and 6 months post administration of the TDV booster or placebo.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The vaccine tested in this study is Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV). This study will look at the long-term antibody persistence and safety of Takeda's TDV in healthy adolescents and adults and will assess the impact of a booster dose.

The study has enrolled 365 healthy participants. Participants who previously received TDV in two parent trials (DEN-304 \[NCT03423173\] and DEN-315 \[NCT03341637\]), will be invited to participate in this follow-up trial. Participants will be assessed for antibody persistence and safety from Baseline (Month 0) through Month 15 (for participants from parent trial DEN-304 \[US\]) or Month 42 (for participants from parent trial DEN-315 \[Mexico\]). At Month 15 (for participants from parent trial DEN-304 \[US\]) or at Month 42 (for participants from parent trial DEN-315 \[Mexico\]), eligible participants will be randomized in 1:1 ratio to one of two trial groups to receive TDV or placebo:

A. Group 1- TDV 0.5 mL subcutaneous (SC) injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico\]).

B. Group 2- Takeda's tetravalent dengue placebo (dummy SC injection - this is a liquid that looks like the study drug but has no active ingredient), 0.5 mL, subcutaneous injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico).

This multi-centre trial will be conducted in US and Mexico. The overall time to participate in this study is up to 21 months for parent trial DEN-304 (US) and up to 48 months for parent trial DEN-315 (Mexico). Participants from parent trial DEN-304 (US) and participants from parent trial DEN-315 (Mexico) will come for 5 visits to the clinic which includes a final visit (Visit 5) 6 months after the booster dose for a follow-up assessment.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Dengue Fever

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The study will be double-blinded, randomized, and placebo-controlled from Month 15 onwards for participants from parent trial DEN-304 (US) and from Month 42 onwards for participants from parent trial DEN-315 (Mexico).

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Prior to Booster: DEN-304

Participants who received TDV in parent trial DEN-304 (US) were assessed before they received booster dose (Placebo/TDV) at Month 15.

Group Type EXPERIMENTAL

Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)

Intervention Type BIOLOGICAL

TDV subcutaneous injection

Prior to Booster: DEN-315

Participants who received TDV in parent trial DEN-315 (Mexico) were assessed before they received booster dose (Placebo/TDV) at Month 42.

Group Type EXPERIMENTAL

Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)

Intervention Type BIOLOGICAL

TDV subcutaneous injection

Booster Phase: Placebo

Participants received TDV placebo-matching 0.5 milliliters (ml) injection, subcutaneous (SC), once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Normal Saline (0.9% NaCl) subcutaneous injection

Booster Phase: TDV

Participants received TDV 0.5 ml, injection, SC, once at Month 15 for participants from parent trial DEN-304 (US) or once at Month 42 for participants from parent trial DEN-315 (Mexico).

Group Type EXPERIMENTAL

Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)

Intervention Type BIOLOGICAL

TDV subcutaneous injection

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)

TDV subcutaneous injection

Intervention Type BIOLOGICAL

Placebo

Normal Saline (0.9% NaCl) subcutaneous injection

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1\. Male or female participants (irrespective of serostatus at baseline in the parent trials (DEN-304 \[(NCT03423173)\] and DEN-315 \[NCT03341637\]) who received at least one dose of Takeda's tetravalent dengue vaccine candidate (TDV) in the parent trials and have data from at least one blood draw post-vaccination.

Exclusion Criteria

1. Participants with a prolonged period of habitation (≥1 year) in a dengue endemic area within the 2 years prior to Visit 1 Day 1 (Month 0).
2. Previous and planned vaccination (during the trial conduct), against any flavivirus including dengue (other than Takeda's TDV), yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.


1. Participants for whom baseline serostatus is not defined in the parent trials (DEN-304 \[(NCT03423173)\] and DEN-315 \[NCT03341637\]).
2. Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
3. Known or suspected impairment/alteration of immune function, including:

1. 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 Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); use of inhaled, intranasal, or topical corticosteroids is allowed.
2. 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 Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US).
3. Administration of immunoglobulins and/or any blood products within the 3 months prior to administration of the TDV booster or placebo at Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); consider whether applicable as an exclusion criterion or criterion for delay.
4. Receipt of immunostimulants within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US).
5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Month 42 for participants from parent trial DEN-315 (Mexico) / Month 15 for participants from parent trial DEN-304 (US).
6. Known human immunodeficiency virus (HIV) infection or HIV-related disease.
7. Hepatitis C virus infection.
8. Genetic immunodeficiency.
4. Abnormalities of splenic or thymic function.
5. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
6. Participants with history of current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a prolonged period of habitation (≥1 year) in a dengue endemic area during trial conduct.
Minimum Eligible Age

13 Years

Maximum Eligible Age

63 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

AES - DRS - Optimal Research Alabama - Huntsville

Huntsville, Alabama, United States

Site Status

AES - DRS - Optimal Research Illinois - Peoria

Peoria, Illinois, United States

Site Status

Alliance for Multispecialty Research, LLC - Newton - PPDS

Newton, Kansas, United States

Site Status

Optima Research

Rockville, Maryland, United States

Site Status

AES - DRS - Synexus Clinical Research US, Inc. Minneapolis

Richfield, Minnesota, United States

Site Status

AES - DRS - Synexus Clinical Research US, Inc. - St. Louis

St Louis, Missouri, United States

Site Status

AES - DRS - Synexus Clinical Research US, Inc. - Omaha

Papillion, Nebraska, United States

Site Status

Advanced Clinical Research/Velocity Clinical Research

West Jordan, Utah, United States

Site Status

Instituto Nacional de Pediatria

Mexico City, , Mexico

Site Status

CAIMED Investigacion en Salud S.A de C.V.

Mexico City, , Mexico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Mexico

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40099800 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2023-000027-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DEN-303

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

TDAP Safety in Pregnant Women
NCT02209623 COMPLETED