Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children

NCT ID: NCT02747927

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 20099 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-26
• Study Completion Date: 2024-06-28

Brief Summary

The main purpose of this study is to evaluate the efficacy of 2 doses of Tetravalent Dengue Vaccine Candidate (TDV) in preventing symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in 4 to 16 year old participants.

Detailed Description

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever and to look at long-term safety results. This study will look at the success rate of TDV in preventing dengue fever (vaccine efficacy) and long-term side effects of the vaccine.

The study will be conducted in 5 parts. Part 1 will evaluate vaccine efficacy (VE) and will last a minimum of 15 months. Part 2 will be for an additional 6 months to evaluate VE. Part 3 will evaluate long-term safety by following participants for side effects and will last an additional 3 years. Part 4 will evaluate safety for 13 months post-booster vaccination. Part 5 will be the long-term safety follow-up for 1 year after completion of Part 4. Participants may be enrolled into a dry-run to commence and test febrile surveillance methodology; this dry-run part may be up to 10 months prior to receiving study injection, however, will not be applicable to all trials sites or participants.

Approximately 20,100 participants will be enrolled into the study and randomly assigned (by chance) to one of the two treatment groups-which will remain undisclosed to the participants and study doctors during the study (unless there is an urgent medical need):

• TDV 0.5 mL subcutaneous injection
• Placebo (dummy inactive subcutaneous injection) - this is a solution that looks like the study drug but has no active ingredient

All participants will receive a single injection of TDV or placebo on Day 1, Day 90. Participation in a booster phase will be offered to approximately 10,500 participants to receive (TDV or placebo) on Day 1b (Day 1 in booster phase). A subset of participants will be asked to record any local symptoms at the injection site (Pain, Erythema and Swelling) in a diary card for 7 days after each injection. The same subset of participants will also be asked to record any systemic symptoms (child <6 years: fever, irritability/fussiness, drowsiness, loss of appetite and child ≥6 years: fever, headache, asthenia, malaise and myalgia) in a diary card for 14 days after each injection.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 7 years excluding the dry-run. Participants will make multiple visits to the clinic and will be contacted at least every week for the entire study duration.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants received placebo-matching TDV, 0.5 milliliters (mL), subcutaneous (SC) injection on Day 1 (Month 0) and Day 90 (Month 3) in Part 1 of the study. Participants eligible for Booster Phase received placebo matching TDV, SC injection on Day 1 booster \[b\] (Month 0b) in Part 4 of the study based on the randomization code applied in Part 1 of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TDV placebo-matching SC injection.

Tetravalent Dengue Vaccine (TDV) 0.5 mL

Participants received TDV, 0.5 mL, SC injection on Day 1 (Month 0) and Day 90 (Month 3) in Part 1 of the study. Participants eligible for Booster Phase received TDV, SC injection on Day 1b (Month 0b) in Part 4 of the study based on the randomization code applied in Part 1 of the study.

Group Type: EXPERIMENTAL

Tetravalent Dengue Vaccine (TDV)

Intervention Type: BIOLOGICAL

TDV SC injection.

Interventions

Placebo

TDV placebo-matching SC injection.

Intervention Type: DRUG

Tetravalent Dengue Vaccine (TDV)

TDV SC injection.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Is aged 4 to 16 years, inclusive, at the time of randomization.

2. 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.

3. The participant and/or the participant's parent/guardian signs and dates an assent/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.

4. Can comply with trial procedures and are available for the duration of follow-up.

1. Is included in the per-protocol set (PPS) of the trial.

2. Was aged 4 to 11 years at the time of randomization in the study (Day 1 [Month 0]).

Exclusion Criteria

1. Has febrile illness (temperature ≥38°C) or moderate or severe acute illness or infection at the time of randomization.

2. Has history of 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.

3. 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).

4. 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.

5. Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.

6. Is first degree relative of individuals involved in trial conduct.

7. 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).

8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination.

9. Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.

10. Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.

11. Identified as an employee of the Investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that Investigator or trial center.

1. Receipt of any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1b (Month 0b), or planning to receive any vaccine within 28 days after Day 1b (Month 0b).

2. Participation in any clinical trial with another investigational product at any time during participation in this trial or intent to participate in another clinical trial at any time during the conduct of the booster phase of this trial.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Universidade Federal Do Espirito Santo Hospital Universitario Cassiano Antonio de Moraes HUCAM

Vitória, Espírito Santo, Brazil

Associacao Obras Sociais Irma Dulce Hospital Santo Antonio

Salvador, Estado de Bahia, Brazil

Universidade Federal de Mato Grosso do Sul

Campo Grande, Mato Grosso do Sul, Brazil

Centro de Estudos e Pesquisa em Molestias Infecciosas LTDA (CPCLIN)

Cidade Alta, Natal - RN, Brazil

Centro de Atencion e Investigacion Medica S.A - CAIMED - Aguazul - PPDS-PV

Aguazul, Casanare Department, Colombia

Centro de Atencion e Investigacion Medica S.A - CAIMED - Yopal - PPDS-PV

Yopal, Casanare Department, Colombia

Centro de Atencion e Investigacion Medica S.A. - CAIMED - Acacias - PPDS-PV

Acacías, Meta Department, Colombia

Centro de Estudios em Infectologia Pediatrica SAS (CEIP S.A.S)

Cali, San Fernando, Colombia

Hospital Maternidad Nuestra Senora de Altagracia

Santo Domingo, Distrito Nacional Santo Domingo, Dominican Republic

Calle Alexander Fleming No. 90 Esquina 37, Ensanche La Fe

Santo Domingo, Distrito Nacional Santo Domingo, Dominican Republic

Universidad Nacional Autonoma de Nicaragua

León, , Nicaragua

Centro De Vacunacion Internacional, S.A. (Cevaxin)

Panama City, , Panama

Centro De Vacunacion Internacional, S.A. (Cevaxin) Sede 24 de Diciembre

Panama City, , Panama

Centro De Vacunacion Internacional, S.A. (Cevaxin) Sede Plaza Carolina

Panama City, , Panama

Centro De Vacunacion Internacional, S.A.(Cevaxin) - La Chorrera

Panama City, , Panama

Dela Salle Health Sciences Institute

Dasmariñas, Cavite, Philippines

Philippines-AFRIMS Virology Research Unit

Cebu City, Cebu, Philippines

Research Institute for Tropical Medicine

City of Muntinlupa, , Philippines

University of the Philippine Manila

Ermita, , Philippines

Las Pinas Health Center A

Las Piñas, , Philippines

Las Pinas Health Center D

Las Piñas, , Philippines

Lady Ridgeway Hospital for Children

Colombo, , Sri Lanka

Colombo South Teaching Hospital

Dehiwala, , Sri Lanka

Negombo General Hospital

Negombo, , Sri Lanka

Colombo North Teaching Hospital

Ragama, , Sri Lanka

The Hospital for Tropical Diseases

Bangkok, Bangkok, Thailand

Phramongkutklao Hospital

Bangkok, Bangkok, Thailand

Srinagarind Hospital

Khon Kaen, , Thailand

Countries

Brazil; Colombia; Dominican Republic; Nicaragua; Panama; Philippines; Sri Lanka; Thailand

References

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)

Borja-Tabora C, Fernando L, Lopez Medina E, Reynales H, Rivera L, Saez-Llorens X, Sirivichayakul C, Yu D, Folschweiller N, Moss KJ, Rauscher M, Tricou V, Zhao Y, Biswal S. Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group. Clin Infect Dis. 2025 Feb 5;80(1):199-206. doi: 10.1093/cid/ciae369.

Reference Type: DERIVED

PMID: 38995684 (View on PubMed)

Sirivichayakul C, Biswal S, Saez-Llorens X, Lopez-Medina E, Borja-Tabora C, Bravo L, Kosalaraksa P, Alera MT, Reynales H, Rivera L, Watanaveeradej V, Yu D, Espinoza F, Dietze R, Fernando L, Wickramasinghe VP, Moreira ED Jr, Fernando AD, Gunasekera D, Luz K, Venancio da Cunha R, Oliveira AL, Rauscher M, Fan H, Borkowski A, Escudero I, Tuboi S, Lloyd E, Tricou V, Folschweiller N, LeFevre I, Vargas LM, Wallace D; TIDES Study Group. Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination. J Infect Dis. 2024 Dec 16;230(6):e1214-e1225. doi: 10.1093/infdis/jiae222.

Reference Type: DERIVED

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Tricou V, Yu D, Reynales H, Biswal S, Saez-Llorens X, Sirivichayakul C, Lopez P, Borja-Tabora C, Bravo L, Kosalaraksa P, Vargas LM, Alera MT, Rivera L, Watanaveeradej V, Dietze R, Fernando L, Wickramasinghe VP, Moreira ED Jr, Fernando AD, Gunasekera D, Luz K, Oliveira AL, Tuboi S, Escudero I, Hutagalung Y, Lloyd E, Rauscher M, Zent O, Folschweiller N, LeFevre I, Espinoza F, Wallace D. Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4.5-year results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Glob Health. 2024 Feb;12(2):e257-e270. doi: 10.1016/S2214-109X(23)00522-3.

Reference Type: DERIVED

PMID: 38245116 (View on PubMed)

Saez-Llorens X, Biswal S, Borja-Tabora C, Fernando L, Liu M, Wallace D, Folschweiller N, Reynales H, LeFevre I; TIDES Study Group. Effect of the Tetravalent Dengue Vaccine TAK-003 on Sequential Episodes of Symptomatic Dengue. Am J Trop Med Hyg. 2023 Mar 6;108(4):722-726. doi: 10.4269/ajtmh.22-0673. Print 2023 Apr 5.

Reference Type: DERIVED

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Rivera L, Biswal S, Saez-Llorens X, Reynales H, Lopez-Medina E, Borja-Tabora C, Bravo L, Sirivichayakul C, Kosalaraksa P, Martinez Vargas L, Yu D, Watanaveeradej V, Espinoza F, Dietze R, Fernando L, Wickramasinghe P, Duarte MoreiraJr E, Fernando AD, Gunasekera D, Luz K, Venancioda Cunha R, Rauscher M, Zent O, Liu M, Hoffman E, LeFevre I, Tricou V, Wallace D, Alera M, Borkowski A. Three-year Efficacy and Safety of Takeda's Dengue Vaccine Candidate (TAK-003). Clin Infect Dis. 2022 Aug 24;75(1):107-117. doi: 10.1093/cid/ciab864.

Reference Type: DERIVED

PMID: 34606595 (View on PubMed)

Biswal S, Borja-Tabora C, Martinez Vargas L, Velasquez H, Theresa Alera M, Sierra V, Johana Rodriguez-Arenales E, Yu D, Wickramasinghe VP, Duarte Moreira E Jr, Fernando AD, Gunasekera D, Kosalaraksa P, Espinoza F, Lopez-Medina E, Bravo L, Tuboi S, Hutagalung Y, Garbes P, Escudero I, Rauscher M, Bizjajeva S, LeFevre I, Borkowski A, Saez-Llorens X, Wallace D; TIDES study group. Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: a randomised, placebo-controlled, phase 3 trial. Lancet. 2020 May 2;395(10234):1423-1433. doi: 10.1016/S0140-6736(20)30414-1. Epub 2020 Mar 17.

Reference Type: DERIVED

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Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b60224db2bf003ab49693?idFilter=%5B%22DEN-301%22%5D

To obtain more information about this study, click this link.

Other Identifiers

U1111-1166-8401

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHRR150522-001010

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-003979-34

Identifier Type: REGISTRY

Identifier Source: secondary_id

DEN-301

Identifier Type: -

Identifier Source: org_study_id