Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults

NCT03746015 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DEN-210
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the neutralizing antibody response against each dengue serotype post-vaccination.

Conditions

Dengue Fever

Keywords

Vaccine

Outcome Measures

Primary Outcomes (10)

• Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test 50% (MNT50).

  Day 15

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 30 (Month 1)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 30 (Month 1)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 60 (Month 2)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 60 (Month 2)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 90 (Month 3)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 90 (Month 3)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 105

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 105

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 120 (Month 4)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 120 (Month 4)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 150 (Month 5)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 150 (Month 5)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 180 (Month 6)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 180 (Month 6)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 270 (Month 9)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 270 (Month 9)

• GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 360 (Month 12)

  GMT of neutralizing antibodies were measured for each of the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT50.

  Day 360 (Month 12)

Secondary Outcomes (12)

• Percentage of Participants With Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Responses to Tetravalent Dengue Vaccine (TDV)

  Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)

• Magnitude of Cellular Immune Response Assessed by Number of Spot Forming Cells [SFC]/10^6 Peripheral Blood Mononuclear Cells (PBMCs) Measured by IFN-γ ELISpot Responses to TDV

  Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)

• Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD4+ T Cells by Intracellular Cytokine Staining (ICS)

  Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)

• Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD8+ T Cells by Intracellular Cytokine Staining (ICS)

  Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)

• Percentage of Participants With Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination

  Days 6, 9, 12, 15, 30 (Month 1), 90 (Month 3), 96, 99, 102, 105, 120 (Month 4)

Study Arms (3)

TDV: Flavivirus-naïve

EXPERIMENTAL

Tetravalent Dengue Vaccine (TDV) 0.5 mL, subcutaneous (SC) injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants who were flavivirus-naïve were included in this group.

Biological: TDV

TDV: DENV Immune: DENV-1 Positive

EXPERIMENTAL

TDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by wild type dengue virus serotype-1 (DENV-1) were included in this group.

Biological: TDV

TDV: DENV Immune: DENV-3 Positive

EXPERIMENTAL

TDV 0.5 mL, SC injection, once on Day 1 (first dose) and then on Day 90 (second dose). Participants with serology consistent with primary infection by DENV-3 were included in this group.

Biological: TDV

Interventions

TDV BIOLOGICAL

TDV subcutaneous injection comprised of 1 molecularly characterized, attenuated dengue virus strain, and 3 chimeric dengue virus strains with potencies of not less than 3.3, 2.7, 4.0, and 4.5 log10 plaque forming units (PFU) per dose of TDV-1, TDV-2, TDV-3, and TDV-4, respectively.

TDV: DENV Immune: DENV-1 Positive; TDV: DENV Immune: DENV-3 Positive; TDV: Flavivirus-naïve

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Who are 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.
• Group 1 only: immunologically naïve to dengue, Zika, Yellow Fever (YF), Japanese Encephalitis (JE), West Nile (WN) (based on negative results for detection of anti-DENV, anti-Zika, anti-YF, anti-JE, anti-WN antibodies) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days \[10 weeks\] prior to Day 1 \[Month 0\]).
• Group 2 only: serology consistent with primary infection with either DENV-1 or DENV-3 (defined as detectable neutralizing antibodies against DENV-1 or DENV-3 only, or titers for DENV-1 or DENV-3 ≥4-times higher than titers for the 2 other dengue serotypes) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days \[10 weeks\] prior to Day 1 \[Month 0\]).

You may not qualify if:

• Has clinically active significant infection (as assessed by the investigator) or body temperature ≥38°C (100.4°F) within 3 days of the intended date of vaccination.
• Has history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
• Known or suspected impairment/alteration of immune function including:
• Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
• Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0).
• Administration of immunoglobulins and/or any blood products within 3 months prior to Day 1 (Month 0) or planned administration during the trial.
• Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
• Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
• Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
• Hepatitis C virus infection.
• Genetic immunodeficiency.
• Has planned vaccination (during the trial conduct) against any non-dengue flavivirus (eg, Zika, YF, JE, WN, tick-borne encephalitis, or Murray-Valley encephalitis).
• Planned travel (during the trial conduct) to any area endemic for dengue.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Optimal Research

Peoria, Illinois, 61614, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 19, 2018
• Study Start: December 28, 2018
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: September 8, 2025
• Results First Posted: April 10, 2024

Record last verified: 2025-08

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

US (2)