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Completed

NCT Number: NCT03746015

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

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

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Key information

Conditions

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

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Optimal Research, Peoria, Illinois, United States

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About this study

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. This study will look at the immunogenicity and safety of TDV in flavivirus-naïve and dengue-immune adults.

The study will enroll approximately 44 patients. Participants will be categorized into two groups based on results from 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 1: Flavivirus-Naïve Participants Group 2: Dengue-Immune Participants

All participants will receive subcutaneous injection of TDV on Day 1 (Month 0) and Day 90 (Month 3).

This trial will be conducted in the United States. The overall time to participate in this study is 12 months. Participants will make multiple visits to the clinic, and 9 months after last dose of study drug for a follow-up assessment.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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]).

Exclusion criteria

  • 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.

Treatment and study plan

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.

Primary outcomes

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

    Time frame: 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).

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

Secondary outcomes

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

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

    IFN-γ ELISpot response >3 times higher compared with baseline (no peptide) and ≥5 spots per 10^6 peripheral blood mononuclear cells (PBMCs) was defined as cellular immune response. Cellular immune response to any peptide pool was reported. The peptide pools included pre-membrane envelope (prME), capsid (C), non-structural proteins (NS): NS1, NS2, NS3, NS4 and NS5 for DENV-1, DENV-2, DENV-3 and DENV-4.

  2. 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

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

    The magnitude of cellular immune response was assessed by the number of SFC/10^6 PBMCs. IFN-γ ELISpot response >3 times higher compared with baseline (no peptide) and ≥5 spots per 10^6 PBMCs was defined as cellular immune response. Cellular immune response to any peptide pool was reported. The peptide pools included prME, C, NS1, NS2, NS3, NS4 and NS5 for DENV-1, DENV-2, DENV-3 and DENV-4.

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

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

    Phenotype characterization of cellular immune response was performed in a subset of participants with IFN- γ ELISPOT responses >50 SFC/10^6 cells and availability of sufficient cells. Markers included cluster of differentiation (CD) 4, CD8, IFN-γ, tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2). The peptide pools included C, NS1, NS2/4, NS3, NS5 for DENV-2 and prME for DENV-1, DENV-2, DENV-3 and DENV-4.

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

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

    Phenotype characterization of cellular immune response was performed in a subset of participants with IFN- γ ELISPOT responses >50 SFC/10^6 cells and availability of sufficient cells. Markers included CD4, CD8, IFN-γ, tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2). The peptide pools included C, NS1, NS2/4, NS3, NS5 for DENV-2 and prME for DENV-1, DENV-2, DENV-3 and DENV-4.

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

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

    Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Percentages were rounded off to the nearest decimal place.

  6. Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination

    Time frame: Up to Day 120 (Month 4)

    The duration of vaccine viremia for each vaccine strain was defined as the date when vaccine viremia was last detected (positive result) to date when vaccine viremia was first detected (positive result) + 1 day. It was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral RNA was detected by qRT-PCR assay. Safety Analysis Set included all participants who received at least 1 dose of trial vaccine.

  7. Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination

    Time frame: Days 6, 9, 12, and 15

    Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral RNA was detected by qRT-PCR assay.

  8. Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination

    Time frame: Within 7 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)

    Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included injection site pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], injection site erythema [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)] and injection site swelling [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)]. Only categories for which there was at least 1 participant are reported.

  9. Percentage of Participants With Solicited Systemic Reactions Following Each Vaccination

    Time frame: Within 14 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)

    Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and will include fever, headache, asthenia, malaise and myalgia. Severity grades are: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). A systemic AE of fever (defined as body temperature ≥ 100.4°F regardless of method taken) was derived from a daily temperature reading recorded within 14 days after vaccination. Only categories for which there was at least 1 participant are reported.

  10. Percentage of Participants With at Least One Unsolicited Adverse Events (AEs) Following Each Vaccination

    Time frame: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose given on Day 1 (Month 0) and 90 (Month 3)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.

  11. Percentage of Participants With Serious Adverse Events (SAEs)

    Time frame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])

    A SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or / significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the aforementioned criteria.

  12. Percentage of Participants With Medically Attended AEs (MAAEs)

    Time frame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])

    MAAEs was defined as AEs leading to a medical visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.

Sponsors and collaborators

Lead sponsor

Takeda

Industry

Registry information

Official study title

An Open-Label, Phase 2 Trial to Investigate the Humoral and Cell-Mediated Immune Responses and Safety of a Tetravalent Dengue Vaccine Candidate (TDV) Administered Subcutaneously in Flavivirus-Naïve and Dengue-Immune Healthy Adults

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Nov 19, 2018
Registry last updated
Sep 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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