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

NCT02747927 | Completed Phase 3 Results DMC

• 4 other identifiers: DEN-301U1111-1166-8401PHRR150522-0010102018-003979-34
• Study Type: interventional
• Target: 20,099
• Locations: 8 countries
• Sites: 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.

Conditions

Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  The VE is defined as 1 - (λv/λc), where λv and λc denote the hazard rates for the TDV and placebo arms, respectively. A virologically-confirmed dengue case is defined as febrile illness (defined as temperature ≥38°C on any 2 of 3 consecutive days) or illness clinically suspected to be dengue by the Investigator with a positive serotype-specific reverse transcriptase polymerase chain reaction (RT-PCR). The primary endpoint of VE was assessed using the number of virologically-confirmed dengue fever cases that occurred during Part 1.

  30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 1 (Month 15) when at least 120 cases of dengue fever were confirmed and minimum duration of participant follow-up was 12 months post-second vaccination

Secondary Outcomes (13)

• VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Each Dengue Serotype

  From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seronegative at Baseline

  From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seropositive at Baseline

  From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Severe Dengue Fever Induced by Any Dengue Serotype

  From 30 days post-second vaccination (Day 120 [Month 4]) until the end of Part 2 (Month 21)

Other Outcomes (34)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  First half of Part 3 (18 months beginning at Month 22)

• VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  Second half of Part 3 (18 months beginning at Month 40)

• VE of Two Doses of TDV in Preventing Hospitalization Due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  First half of Part 3 (18 months beginning at Month 22)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Tetravalent Dengue Vaccine (TDV) 0.5 mL

EXPERIMENTAL

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.

Biological: Tetravalent Dengue Vaccine (TDV)

Interventions

Placebo DRUG

TDV placebo-matching SC injection.

Placebo

Tetravalent Dengue Vaccine (TDV) BIOLOGICAL

TDV SC injection.

Tetravalent Dengue Vaccine (TDV) 0.5 mL

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Is aged 4 to 16 years, inclusive, at the time of randomization.
• 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.
• 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.
• Can comply with trial procedures and are available for the duration of follow-up.
• Is included in the per-protocol set (PPS) of the trial.
• Was aged 4 to 11 years at the time of randomization in the study (Day 1 \[Month 0\]).

You may not qualify if:

• Has febrile illness (temperature ≥38°C) or moderate or severe acute illness or infection at the time of randomization.
• 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.
• 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).
• 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.
• Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
• Is first degree relative of individuals involved in trial conduct.
• 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).
• Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination.
• Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (28)

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

Vitória, Espírito Santo, 29040-091, Brazil

Location

Associacao Obras Sociais Irma Dulce Hospital Santo Antonio

Salvador, Estado de Bahia, 40415-000, Brazil

Location

Universidade Federal de Mato Grosso do Sul

Campo Grande, Mato Grosso do Sul, 79070-900, Brazil

Location

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

Cidade Alta, Natal - RN, 59025-050, Brazil

Location

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

Aguazul, Casanare Department, Colombia

Location

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

Yopal, Casanare Department, Colombia

Location

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

Acacías, Meta Department, 507001, Colombia

Location

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

Cali, San Fernando, Colombia

Location

Hospital Maternidad Nuestra Senora de Altagracia

Santo Domingo, Distrito Nacional Santo Domingo, 10204, Dominican Republic

Location

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

Santo Domingo, Distrito Nacional Santo Domingo, 10514, Dominican Republic

Location

Universidad Nacional Autonoma de Nicaragua

León, Nicaragua

Location

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

Panama City, 10662, Panama

Location

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

Panama City, Panama

Location

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

Panama City, Panama

Location

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

Panama City, Panama

Location

Dela Salle Health Sciences Institute

Dasmariñas, Cavite, 4114, Philippines

Location

Philippines-AFRIMS Virology Research Unit

Cebu City, Cebu, 6000, Philippines

Location

Research Institute for Tropical Medicine

City of Muntinlupa, 1781, Philippines

Location

University of the Philippine Manila

Ermita, 1000, Philippines

Location

Las Pinas Health Center A

Las Piñas, Philippines

Location

Las Pinas Health Center D

Las Piñas, Philippines

Location

Lady Ridgeway Hospital for Children

Colombo, 00800, Sri Lanka

Location

Colombo South Teaching Hospital

Dehiwala, 10250, Sri Lanka

Location

Negombo General Hospital

Negombo, 11500, Sri Lanka

Location

Colombo North Teaching Hospital

Ragama, 11010, Sri Lanka

Location

The Hospital for Tropical Diseases

Bangkok, Bangkok, 10270, Thailand

Location

Phramongkutklao Hospital

Bangkok, Bangkok, 10400, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Related Publications (8)

• 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.

  PMID: 40099800 DERIVED

• 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.

  PMID: 38995684 DERIVED

• 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.

  PMID: 38682569 DERIVED

• 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.

  PMID: 38245116 DERIVED

• 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.

  PMID: 36878213 DERIVED

• 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.

  PMID: 34606595 DERIVED

• 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.

  PMID: 32197105 DERIVED

• Biswal S, Reynales H, Saez-Llorens X, Lopez P, Borja-Tabora C, Kosalaraksa P, Sirivichayakul C, Watanaveeradej V, Rivera L, Espinoza F, Fernando L, Dietze R, Luz K, Venancio da Cunha R, Jimeno J, Lopez-Medina E, Borkowski A, Brose M, Rauscher M, LeFevre I, Bizjajeva S, Bravo L, Wallace D; TIDES Study Group. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med. 2019 Nov 21;381(21):2009-2019. doi: 10.1056/NEJMoa1903869. Epub 2019 Nov 6.

  PMID: 31693803 DERIVED

Related Links

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

MeSH Terms

Interventions

Dengue Vaccines

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 22, 2016
• Study Start: April 26, 2016
• Primary Completion: July 11, 2018
• Study Completion: June 28, 2024
• Last Updated: November 19, 2025
• Results First Posted: August 18, 2021

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

PH (6); DO (2); CO (4); BR (4); PA (4); SR (4); TH (3); NI (1)