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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02747927
Recruitment Status : Active, not recruiting
First Posted : April 22, 2016
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Biological: TDV Drug: Placebo Phase 3

Detailed Description:

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 and to look at long-term safety results. This study will look at the success rate of TDV in preventing dengue fever (vaccine efficacy) and long-term side effects of the vaccine.

The study will be conducted in 5 parts. Part 1 will evaluate vaccine efficacy (VE) and will last a minimum of 15 months. Part 2 will be for an additional 6 months to evaluate VE. Part 3 will evaluate long-term safety by following participants for side effects and will last an additional 3 years. Part 4 will evaluate safety for 13 months post-booster vaccination. Part 5 will be the long-term safety follow-up for 1 year after completion of Part 4. Participants may be enrolled into a dry-run to commence and test febrile surveillance methodology; this dry-run part may be up to 10 months prior to receiving study injection, however, will not be applicable to all trials sites or participants.

Approximately 20,100 participants will be enrolled into the study and randomly assigned (by chance) to one of the two treatment groups-which will remain undisclosed to the participants and study doctors during the study (unless there is an urgent medical need):

  • TDV 0.5 mL subcutaneous injection
  • Placebo (dummy inactive subcutaneous injection) - this is a solution that looks like the study drug but has no active ingredient

All participants will receive a single injection of TDV or placebo on Day 1, Day 90. Participation in a booster phase will be offered to approximately 10,500 participants to receive (TDV or placebo) on Day 1b (Day 1 in booster phase). A subset of participants will be asked to record any local symptoms at the injection site (Pain, Erythema and Swelling) in a diary card for 7 days after each injection. The same subset of participants will also be asked to record any systemic symptoms (child <6 years: fever, irritability/fussiness, drowsiness, loss of appetite and child ≥6 years: fever, headache, asthenia, malaise and myalgia) in a diary card for 14 days after each injection.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 7 years excluding the dry-run. Participants will make multiple visits to the clinic and will be contacted at least every week for the entire study duration.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Investigate the Efficacy, Safety and Immunogenicity of a Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in Healthy Children Aged 4 - 16 Years Old
Study Start Date : September 7, 2016
Actual Primary Completion Date : July 11, 2018
Estimated Study Completion Date : March 21, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue Fever

Arm Intervention/treatment
Experimental: Tetravalent Dengue Vaccine
Tetravalent Dengue Vaccine (TDV) 0.5 mL, subcutaneous (SC) injection on Day 1 and Day 90. Eligible participants will offered TDV, SC injection, on Day 1 in the Booster Phase (Day 1b) based on the randomization on Day 1 of the study.
Biological: TDV
TDV SC injection.

Placebo Comparator: Placebo
Placebo-matching TDV, 0.5 mL, SC injection on Day 1 and Day 90. Eligible participants will be offered a placebo-matching TDV, SC injection on Day 1b in Booster Phase based on the randomization on Day 1 of the study.
Drug: Placebo
TDV placebo-matching SC injection.




Primary Outcome Measures :
  1. Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype [ Time Frame: 30 days post-second vaccination (Day 120) until the end of Part 1 (120 cases of dengue fever are confirmed and minimum duration of participant follow-up of 12 months post-second vaccination) ]

    VE 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).



Secondary Outcome Measures :
  1. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Each Dengue Serotype [ Time Frame: From 30 days post-second vaccination (Day 120) until the end of Part 2 (up to 21 months) ]

    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).


  2. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seronegative at Baseline [ Time Frame: From 30 days post-second vaccination (Day 120) until the end of Part 2 (up to 21 months) ]

    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).


  3. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seropositive at Baseline [ Time Frame: From 30 days post-second vaccination (Day 120) until the end of Part 2 (up to 21 months) ]

    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).


  4. VE of Two Doses of TDV in Preventing Hospitalization due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype [ Time Frame: From 30 days post-second vaccination (Day 120) until the end of Part 2 (up to 21 months) ]

    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).


  5. VE of Two Doses of TDV in Preventing Virologically-Confirmed Severe Dengue Fever Induced by Any Dengue Serotype [ Time Frame: From 30 days post-second vaccination (Day 120) until the end of Part 2 (up to 21 months) ]

    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).


  6. Percentage of Participants with Solicited Local Injection Site Adverse Events (AEs) by Severity in the Safety Subset [ Time Frame: Days 1 through 7 after each vaccination ]
    Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days after each vaccination.

  7. Percentage of Participants with Solicited Systemic Adverse Events (AEs) by Severity in the Safety Subset [ Time Frame: Days 1 through 14 after each vaccination ]
    Solicited systemic AEs in children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite that occurred within 14 days after each vaccination. Solicited systemic AEs in children (≥ 6 years) are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination.

  8. Severity of Solicited Systemic Adverse Events (AEs) in the Safety Subset [ Time Frame: Days 1 through 14 after each vaccination ]
    Solicited systemic AEs in children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite that occurred within 14 days after each vaccination. Solicited systemic AEs in children (≥ 6 years) are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination.

  9. Percentage of Participants with Any Unsolicited Adverse Events (AEs) in the Safety Subset [ Time Frame: Days 1 through 28 after each vaccination ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration. Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.

  10. Percentage of Participants with Serious Adverse Events (SAEs) During Parts 1 and 2 [ Time Frame: From Day 1 until the end of Parts 1 and 2 (approximately 21 months) ]
    A serious adverse event (SAE) is 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 above mentioned criteria.

  11. Percentage of Participants with Fatal SAEs and SAEs Related to Study Drug During the First and Second Half of Part 3 [ Time Frame: First and Second half (18 months each) of Part 3 (up to 3 years, beginning at Month 22) ]
    A serious adverse event (SAE) is 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 above mentioned criteria.

  12. Percentage of Participants with a Seropositive Response for Each of the Four Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Prevaccination on Day 1, post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years) ]
    Seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.

  13. Percentage of Participants with a Seropositive Response for Multiple Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Prevaccination on Day 1, post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years) ]
    Seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.

  14. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Prevaccination on Day 1, post-first vaccination on Month 1, pre-vaccination on Month 3; post-second vaccination at Months 4, 9 and 15, and then annually (up to 3 years) ]
    GMTs of neutralizing antibodies will be measured via microneutralization test 50% (MNT50). The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Is aged 4 to 16 years, inclusive, at the time of randomization.
  2. 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.
  3. 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.
  4. Can comply with trial procedures and are available for the duration of follow-up.

Inclusion criteria for Booster Phase:

  1. Is included in the per-protocol set (PPS) of the trial.
  2. Was aged 4 to 11 years at the time of randomization in the study (Day 1 [Month 0]).

Exclusion Criteria:

  1. Has febrile illness (temperature ≥38°C) or moderate or severe acute illness or infection at the time of randomization.
  2. 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.
  3. 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).
  4. 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.
  5. Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
  6. Is first degree relative of individuals involved in trial conduct.
  7. 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).
  8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks post-second vaccination.
  9. Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
  10. Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
  11. 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.

Exclusion criteria for Booster Phase:

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02747927


Locations
Show Show 28 study locations
Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Director: Medical Director Clinical Science Takeda
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02747927    
Other Study ID Numbers: DEN-301
U1111-1166-8401 ( Registry Identifier: WHO )
PHRR150522-001010 ( Registry Identifier: PHRR )
2018-003979-34 ( Registry Identifier: EudraCT )
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/takeda/
Keywords provided by Takeda:
Drug therapy
Additional relevant MeSH terms:
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Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral