A Study of Dengue Vaccine in Healthy Children, Teenagers and Adults in India

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (Live, Attenuated) (TDV) Administered Subcutaneously to Healthy Subjects Aged 4 to 60 Years in India

The main aims of the study are to learn about side effects and a participant's immune response to Takeda's Dengue Vaccine when given twice within 3 months.

Participants will receive 2 doses of their randomized treatment (vaccine or placebo). Children, teenagers and adults will receive one dose of either the vaccine or placebo on Day 1 and the second dose of either the vaccine or placebo 3 months later. Up to 4 blood samples will be taken throughout the study.

During the study, participants will visit their study clinic 6 times.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: TDV; Biological: Placebo

Detailed Description

The vaccine being tested in this study is called TDV (Live, Attenuated). TDV is being tested to prevent dengue. This study will assess the safety and immunogenicity of TDV in healthy participants.

The study will enroll approximately 480 patients. Participants will be randomly assigned (by chance, like flipping a coin) to receive either TDV or placebo- which will remain undisclosed to the participant, and investigator during the study:

• Cohort 1, ≥18 to ≤60 Age Group: TDV
• Cohort 1, ≥18 to ≤60 Age Group: Placebo
• Cohort 2, ≥4 to <18 Age Group: TDV
• Cohort 2, ≥4 to <18 Age Group: Placebo

This multi-center trial will be conducted in India. The overall duration of the study is approximately 9 months.

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Bhubaneswar, India, 751003
    • Preventive and Therapeutic Clinical Trial Unit (PTCTU), Dept. of Community Medicine, Institute of Medical Science and SUM Hospital, K-8, Kalinga Nagar
  • Kattankulathur, India, 603203
    • SRM Medical College Hospital & Research Centre, SRM Nagar, Potheri
  • Kolkata, India, 700020
    • IPGME&R and SSKM Hospital, 244 AJC Bose Road
  • Lucknow, India, 226003
    • King George's Medical University, Department of Medicine, Chowk
  • Nashik, India, 422003
    • Suyog Hospital, 2nd Floor, B-Wing, Krushi Utpanna Bazar, Samiti Sankul, Dindori Rd, Panchavati
  • New Delhi, India, 110002
    • Maulana Azad Medical College & Associated Lok Nayak, Govind Ballabh Pant Hospitals and Guru Nanak Eye Center
  • Pune, India, 411011
    • KEM Hospital Research Centre, Sandar Moodliar Road, Rasta Peth
  • Visakhapatnam, India, 530002
    • King George Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560060
      • BGS Global Institute of Medical Sciences (BGS-GIMS) #67, BGS Health & Education City, Uttarahalli Main Road, Kengeri
  • Tamil Nadu
    • Pudupākkam, Tamil Nadu, India, 603 103
      • Chettinad Academy of Research and Education, Chettinad Health City, SH,49A, Dist. Kelambakkam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Participants who can comply with trial procedures and are available for the duration of follow-up.

Key Exclusion Criteria:

At screening and at vaccination:

1. A body mass index (BMI) ≥35 kg/m^2.
2. Intent to participate in another clinical trial at any time during the conduct of this trial.

3. Plans to receive any of the following:

   1. A licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to TDV or placebo administration.
   2. A coronavirus vaccine within 14 days prior to TDV or placebo administration.
   3. A vaccine authorized for emergency use within 28 days of TDV or placebo administration.
4. Known substance or alcohol abuse within the past 2 years that may interfere with his/her ability to comply with requirements for trial participation.
5. Receipt of previous vaccination against dengue virus.
6. Previous participation in any clinical trial of a dengue candidate vaccine.

At Vaccination:

1. Participants with febrile illness or moderate or severe acute illness, or infection, at the time of random assignment.
2. Participants medicated with antipyretic and/or analgesic medication(s) within 24 hours prior to TDV or placebo administration.

NOTE: Other protocol defined Inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: ≥18 to ≤60 Years Age Group: TDV; Participants received TDV subcutaneous (SC) injection on Day 1 (Month 0) and Day 90 (Month 3) of the study.	Biological: TDV; TDV SC injection on Day 1 and Day 90 of the study; Other Names: TAK-003
Placebo Comparator: Cohort 1: ≥18 to ≤60 Years Age Group: Placebo; Participants received TDV-matching placebo SC injection on Day 1 (Month 0) and Day 90 (Month 3) of the study.	Biological: Placebo; Normal Saline (0.9% NaCl) SC injection on Day 1 and Day 90 of the study
Experimental: Cohort 2: ≥4 to <18 Years Age Group: TDV; Participants received TDV SC injection on Day 1 (Month 0) and Day 90 (Month 3) of the study.	Biological: TDV; TDV SC injection on Day 1 and Day 90 of the study; Other Names: TAK-003
Placebo Comparator: Cohort 2: ≥4 to <18 Years Age Group: Placebo; Participants received TDV-matching placebo SC injection on Day 1 (Month 0) and Day 90 (Month 3) of the study.	Biological: Placebo; Normal Saline (0.9% NaCl) SC injection on Day 1 and Day 90 of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity Within 7 Days Post-vaccination at Day 1 for Age Group Less Than 6 Years	Solicited local AEs at injection site were defined as injection site pain, injection site erythema, and injection site swelling. The AEs were graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe based on solicited safety parameters defined for infant/toddler/child (<6 years of age).	Within 7 days post-vaccination at Day 1
Number of Participants With Solicited Local (Injection Site) AEs by Severity Within 7 Days Post-vaccination at Day 1 for Age Group 6 Years and Over	Solicited local AEs at injection site were defined as injection site pain, injection site erythema, and injection site swelling. The AEs were graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe based on solicited safety parameters defined for child/adolescent/adult (≥6 years of age).	Within 7 days post-vaccination at Day 1
Number of Participants With Solicited Local (Injection Site) AEs by Severity Within 7 Days Post-vaccination at Day 90 for Age Group Less Than 6 Years	Solicited local AEs at injection site were defined as injection site pain, injection site erythema, and injection site swelling. The AEs were graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe based on solicited safety parameters defined for infant/toddler/child (<6 years of age).	Within 7 days post-vaccination at Day 90
Number of Participants With Solicited Local (Injection Site) AEs by Severity Within 7 Days Post-vaccination at Day 90 for Age Group 6 Years and Over	Solicited local AEs at injection site were defined as injection site pain, injection site erythema, and injection site swelling. The AEs were graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe based on solicited safety parameters defined for child/adolescent/adult (≥6 years of age).	Within 7 days post-vaccination at Day 90
Number of Participants With Solicited Systemic AEs by Severity Within 14 Days Post-vaccination at Day 1 for Age Group Less Than 6 Years	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. Solicited systemic AEs assessments for children <6 years old comprised: irritability/fussiness, drowsiness, loss of appetite (graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe) and fever in °C (collected by temperature ranges as indicated).	Within 14 days post-vaccination at Day 1
Number of Participants With Solicited Systemic AEs by Severity Within 14 Days Post-vaccination at Day 1 for Age Group 6 Years and Over	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. Solicited systemic AEs assessments for children ≥ 6 years old/adolescents/adults comprised: headache, asthenia, malaise, myalgia (graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe) and fever in °C (collected by temperature ranges as indicated).	Within 14 days post-vaccination at Day 1
Number of Participants With Solicited Systemic AEs by Severity Within 14 Days Post-vaccination at Day 90 for Age Group Less Than 6 Years	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. Solicited systemic AEs assessments for children <6 years old comprised: drowsiness, irritability/fussiness, loss of appetite (graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe). Data for drowsiness, irritability/fussiness and loss of appetite has been reported in this outcome measure.	Within 14 days post-vaccination at Day 90
Number of Participants With Solicited Systemic AEs of Fever by Severity Within 14 Days Post-vaccination at Day 90 for Age Group Less Than 6 Years	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. Solicited systemic AEs assessments for children <6 years old also comprised of fever in °C (collected by temperature ranges as indicated). Data for fever has been reported in this outcome measure.	Within 14 days post-vaccination at Day 90
Number of Participants With Solicited Systemic AEs by Severity Within 14 Days Post-vaccination at Day 90 for Age Group 6 Years and Over	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. Solicited systemic AEs assessments for children ≥ 6 years old/adolescents/adults comprised: headache, asthenia, malaise, myalgia (graded by investigator as Grade 0: none, Grade 1: mild, Grade 2: moderate and Grade 3: severe) and fever in °C (collected by temperature ranges as indicated).	Within 14 days post-vaccination at Day 90
Percentage of Participants With Any Unsolicited AEs Within 28 Days Post-vaccination at Day 1	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.	Within 28 days post-vaccination at Day 1
Percentage of Participants With Any Unsolicited AEs Within 28 Days Post-vaccination at Day 90	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.	Within 28 days post-vaccination at Day 90
Percentage of Participants With an AE Leading to Participant Withdrawal From Trial	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.	From first vaccination on Day 1 through the end of trial (up to Day 270)
Percentage of Participants With an AE Leading to TDV or Placebo Discontinuation	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.	From first vaccination on Day 1 through the end of trial (up to Day 270)
Percentage of Participants With a Medically-attended AE (MAAE)	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.	From first vaccination on Day 1 through the end of trial (up to Day 270)
Percentage of Participants With a Serious Adverse Event (SAE)	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. 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, is an important medical event.	From first vaccination on Day 1 through the end of trial (up to Day 270)
GMTs of Neutralizing Antibodies by Microneutralization Test (MNT50) for Each of the 4 Dengue Virus Serotypes at Day 120	GMTs of neutralizing antibodies were measured by microneutralization test 50% (MNT50) for each of the 4 dengue serotypes for all participants. The 4 dengue virus serotypes (DENV) are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 120 (Month 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroconversion for Each of the 4 Dengue Virus Serotypes	Seroconversion rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositive is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 120 and Day 270
Percentage of Participants With Seroconversion for Multiple (2, 3, or 4) Dengue Virus Serotypes	Seroconversion rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositive is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1, Day 120 and Day 270
GMTs by MNT50 Against Each of the 4 Dengue Virus Serotypes at Day 1 and Day 270	GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 dengue serotypes for all participants. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.	Day 1 and 270

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2024
• Primary Completion (Actual): May 5, 2025
• Study Completion (Actual): May 5, 2025

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: DEN-302; 2023-000134-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No