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

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ClinicalTrials.gov Identifier: NCT02747927
Recruitment Status : Active, not recruiting
First Posted : April 22, 2016
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The 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: Takeda's Tetravalent Dengue Vaccine Candidate Drug: TDV 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 3 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. Participants may be enrolled into a dry-run to commence and test febrile surveillance methodology; this dry-run part may be upto 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 on Day 1 and Day 90. 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 4.75 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.


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 : December 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue

Arm Intervention/treatment
Experimental: Tetravalent Dengue Vaccine Candidate
Takeda's Tetravalent Dengue Vaccine Candidate (TDV) 0.5 mL, subcutaneous injection on Day 1 and Day 90.
Biological: Takeda's Tetravalent Dengue Vaccine Candidate
TDV subcutaneous injection

Placebo Comparator: Placebo
Placebo-matching TDV, 0.5 mL, subcutaneous injection on Day 1 and Day 90.
Drug: TDV Placebo
Takeda's TDV placebo-matching vaccine




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 subject 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) 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. Severity of Solicited Local Injection Site Adverse Events (AEs) 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.

  8. Percentage of Participants with 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. 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.

  10. Percentage of Participants with Any Unsolicited Adverse Events (AEs) in the Safety Subset [ Time Frame: Days 1 through 28 after each vaccination ]
    Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.

  11. 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.

  12. Percentage of Participants with Fatal SAEs and SAEs Related to Study Drug During the First and Second Half of Part 3 [ Time Frame: For 3 years (18 month halves) beginning at the end of Part 2 (approximately 21 months after the first vaccination) ]
    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.

  13. Percentage of Participants with a Seropositive Response for Each of the Four Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Day 1 and Months 1, 3, 4, 9, 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. Percentage of Participants with a Seropositive Response for Multiple Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Day 1 and Months 1, 3, 4, 9, 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.

  15. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four Dengue Serotypes in the Immunogenicity Subset [ Time Frame: Day 1 and Months 1, 3, 4, 9, 15 and then annually (up to 3 years) ]
    GMTs of neutralizing antibodies will be measured via microneutralization test (MNT). 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.


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.

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.

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
Brazil
Universidade Federal Do Espirito Santo Hospital Universitario Cassiano Antonio de Moraes HUCAM
Vitoria, Espirito Santo, Brazil
Universidade Federal de Mato Grosso do Sul
Campo Grande, Mato Grosso Do Sul, Brazil
Associacao Obras Sociais Irma Dulce Hospital Santo Antonio
Bahia, Salvador, Brazil, 40420-000
Hospital infantil Varela Santiago
Natal, Brazil
Colombia
Centro de Atencion e Investigacion Medica (CAIMED) Aguazul
Aguazul, Casanare, Colombia
Centro de Atencion e Investigacion Medica (CAIMED) Yopal
Yopal, Casanare, Colombia
Centro de Atencion e Investigacion Medica (CAIMED) Acacias
Acacias, Meta, Colombia, 507001
Centro de Estudios em Infectologia Pediatrica SAS
Cali, Colombia
Dominican Republic
Hospital Maternidad Nuestra Senora de la Altagracia
Santo Domingo, Dominican Republic, 10205
Centro de Atencion E Investigacion Medica (CAIMED)
Santo Domingo, Dominican Republic
Nicaragua
Universidad Nacional Autonoma de Nicaragua (UNAN) Leon
Leon, Nicaragua
Panama
Centro De Vacunacion Internacional, S.A.(Cevaxin) - La Chorrera
Ciudad de Panama, Panama
Centro De Vacunacion Internacional, S.A.(Cevaxin) - Plaza Carolina
Ciudad de Panama, Panama
Centro De Vacunacion Internacional, S.A.(CEVAXIN)
Panama City, Panama, 10662
Centro De Vacunacion Internacional, S.A.(Cevaxin) - 24 de Diciembre
Tocumen, Panama
Philippines
Dela Salle Health Sciences Institute
Cavite, Philippines, 4114
Philippines AFRIMS Virology Research Unit (PAVRU)
Cebu City, Philippines, 6000
Las Pinas Health Center A
Las Pinas City, Philippines
Las Pinas Health Center D
Las Pinas City, Philippines
National Institutes of Health, University of the Philippines Manila
Manila, Philippines
Research Institute for Tropical Medicine
Muntinlupa City, Philippines, 1781
Sri Lanka
Colombo South Teaching Hospital
Gangodawila, Nugegoda, Sri Lanka, 10250
Lady Ridgeway Hospital for Children
Colombo, Sri Lanka, 00800
Negombo General Hospital
Negombo, Sri Lanka, 11500
Colombo North Teaching Hospital
Ragama, Sri Lanka, 11010
Thailand
Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand, 10400
Phramongkutklao Hospital
Bangkok, Thailand, 10400
Srinagarind Hospital
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Clinical Science Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02747927     History of Changes
Other Study ID Numbers: DEN-301
U1111-1166-8401 ( Registry Identifier: WHO )
PHRR150522-001010 ( Registry Identifier: PHRR )
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: September 2018

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs