Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in Singapore

NCT02425098 | Completed Phase 2 Results DMC

• 2 other identifiers: DEN-205U1111-1166-8884
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Dengue Fever

Keywords

Vaccine

Outcome Measures

Primary Outcomes (10)

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

  GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test \[MNT\].

  Day 15

• Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30

  GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  Day 30

• Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90

  GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  Day 90

• Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180

  GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  Day 180

• Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365

  GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  Day 365

• Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15

  Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  Day 15

• Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30

  Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  Day 30

• Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90

  Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  Day 90

• Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180

  Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  Day 180

• Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365

  Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  Day 365

Secondary Outcomes (9)

• Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity

  Within 7 days after Vaccination

• Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity

  Within 14 days after Vaccination

• Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination

  Within 28 days after Vaccination

• Number of Participants With Serious Adverse Events (SAEs)

  From first vaccination through end of study (Day 365)

• Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status

  Days 15, 30, 90, 180 and 365

Study Arms (2)

High-dose Tetravalent Dengue Vaccine (HD-TDV)

EXPERIMENTAL

High-dose Tetravalent Dengue Vaccine \[HD-TDV\], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2\*10\^4 plaque forming units (PFU), 5\*10\^4 PFU, 1\*10\^5 PFU, and 3\*10\^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.

Biological: Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)

Tetravalent Dengue Vaccine (TDV)

EXPERIMENTAL

Tetravalent Dengue Vaccine \[TDV\], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2\*10\^4 plaque forming units (PFU), 5\*10\^3 PFU, 1\*10\^5 PFU, and 3\*10\^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.

Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Interventions

Takeda's Tetravalent Dengue Vaccine Candidate (TDV) BIOLOGICAL

TDV subcutaneous injection

Tetravalent Dengue Vaccine (TDV)

Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV) BIOLOGICAL

High-dose TDV subcutaneous injection

High-dose Tetravalent Dengue Vaccine (HD-TDV)

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant signs and dates a 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.
• Is aged 21 to 45 years of age, inclusive.
• 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.
• Can comply with trial procedures and are available for the duration of follow-up.
• Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.

You may not qualify if:

• Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
• Has history 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, including but not limited to:
• Known hypersensitivity or allergy to any of the vaccine components.
• Female participants who are pregnant or breastfeeding.
• Individuals with any serious chronic or progressive disease according to judgment of the Investigator (e.g. neoplasm, insulin-dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome).
• Known or suspected impairment/alteration of immune function, including:
• i. 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 Day 1 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
• ii. 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 Day 1 (Month 0).
• iii. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
• iv. Receipt of immunostimulants within 60 days prior to Day 1(Month 0).
• v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
• vi. Human immunodeficiency virus (HIV) infection and HIV-related diseases.
• vii. Hepatitis C virus (HCV) infection.
• viii. Genetic immunodeficiency.
• 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).

Sponsors & Collaborators

• Takeda: lead

Study Sites (3)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Related Publications (4)

• 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

• White LJ, Young EF, Stoops MJ, Henein SR, Adams EC, Baric RS, de Silva AM. Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003). PLoS Negl Trop Dis. 2021 Mar 12;15(3):e0009258. doi: 10.1371/journal.pntd.0009258. eCollection 2021 Mar.

  PMID: 33711074 DERIVED

• Michlmayr D, Andrade P, Nascimento EJM, Parker A, Narvekar P, Dean HJ, Harris E. Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine. J Infect Dis. 2021 Feb 3;223(2):247-257. doi: 10.1093/infdis/jiaa346.

  PMID: 32572472 DERIVED

• Tricou V, Low JG, Oh HM, Leo YS, Kalimuddin S, Wijaya L, Pang J, Ling LM, Lee TH, Brose M, Hutagalung Y, Rauscher M, Borkowski A, Wallace D. Safety and immunogenicity of a single dose of a tetravalent dengue vaccine with two different serotype-2 potencies in adults in Singapore: A phase 2, double-blind, randomised, controlled trial. Vaccine. 2020 Feb 5;38(6):1513-1519. doi: 10.1016/j.vaccine.2019.11.061. Epub 2019 Dec 13.

  PMID: 31843269 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: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  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: 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 9, 2015
• First Posted: April 23, 2015
• Study Start: June 3, 2015
• Primary Completion: September 18, 2017
• Study Completion: September 18, 2017
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-07

Locations

SG (3)