Home » Trials » SLCTR/2016/019


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 -

SLCTR Registration Number

SLCTR/2016/019


Date of Registration

22 Jul 2016

The date of last modification

Aug 24, 2018


Trial Status



Application Summary


Scientific Title of Trial

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


Public Title of Trial

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


Disease of Health Condition(s) Studied

Dengue fever


Scientific Acronym

TIDES (Tetravalent Immunization against Dengue Efficacy Study)


Public Acronym

TIDES (Tetravalent Immunization against Dengue Efficacy Study)


Brief title

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


Universal Trial Number

U1111-1166-8401 [Registry ID: WHO]


Any other number(s) assigned to the trial and issuing authority

PHRR150522-001010 [Registry ID: PHRR],NCT02747927 [Registry ID: Clinicaltrials.gov], DEN-301 [trial identifier assigned by Takeda Vaccines]


Trial Details


What is the research question being addressed?

Is the Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in Healthy Children Aged 4 – 16 Years Old, safe and effective in preventing symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Prevention


Purpose

Phase 3


Intervention(s) planned

Study sites i. Colombo North Teaching Hospital ii. Colombo South Teaching Hospital iii. Lady Ridgeway Hospital for Children iv. Negombo General Hospital

Method of randomization:
Randomization ratio of 2:1 (TDV: placebo) using an interactive system (Interactive Web Response System [IWRS] or Interactive Voice Response System [IVRS])

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

Arm 2: Placebo Comparator: Placebo Placebo-matching TDV, 0.5 mL, subcutaneous injection on Day 1 and Day 90. Assigned Interventions: Drug: TDV Placebo Takeda’s TDV placebo-matching vaccine. Part 1 of the study would be complete when 120 cases of dengue fever are confirmed with a minimum duration of subject follow-up of 12 months post-second vaccination.


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.


Primary outcome(s)

  1. Vaccine Efficacy (VE) of Two Doses of Tetravalent Dengue Vaccine Candidate (TDV) in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

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).


Primary outcome(s) - Time of assessment(s)

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)


Secondary outcome

  1. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Each Dengue Serotype

  2. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seronegative at Baseline

  3. VE of Two Doses of TDV in Preventing Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype in Participants Dengue Seropositive at Baseline

  4. VE of Two Doses of TDV in Preventing Hospitalization due to Virologically-Confirmed Dengue Fever Induced by Any Dengue Serotype

  5. VE of Two Doses of TDV in Preventing Virologically-Confirmed Severe Dengue Fever Induced by Any Dengue Serotype

  6. Percentage of Participants with Solicited Local Injection Site Adverse Events (AEs) in the Safety Subset 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 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 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 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 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 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 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 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 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 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.


Secondary outcome(s) - Time of assessment(s)

  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 (additional 6 months following the completion of Part 1)]

  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 (additional 6 months following the completion of Part 1)]

  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 (additional 6 months following the completion of Part 1)]

  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 (additional 6 months following the completion of Part 1)]

  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 (additional 6 months following the completion of Part 1)]

  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]

  7. Severity of Solicited Local Injection Site Adverse Events (AEs) in the Safety Subset [Time Frame: Days 1 through 7 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]

  9. Severity of Solicited Systemic Adverse Events (AEs) in the Safety Subset [Time Frame: Days 1 through 14 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]

  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)]

  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)]

  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]

  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]

  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]



Target number/sample size

2100 subjects in Sri Lanka (Ratio 2:1: 1400 in TDV arm, 700 in placebo arm), 20100 subjects globally


Countries of recruitment

Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, Thailand, Viet Nam


Anticipated start date

2016-08-19


Anticipated end date

2022-07-22


Recruitment status

Complete


State of ethics review approval

Approved by the Ethics Review Committee, Faculty of Medical Sciences, University of Sri Jayewardenepura on 08 June 2016 (Ref: 19.15)


Funding source

Takeda Vaccines Inc., USA



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. LakKumar Fernando
Consultant Paediatrician
Center for Clinical Management of Dengue and Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka
Tel : +94777357565


lakkumar@gmail.com

Contact Person for Public Queries

Dr Hasitha Tissera
Consultant Epidemiologist
Epidemiology Unit, Ministry of Health, Nutrition and Indigenous Medicine 231, De Saram Place, Colombo, Sri Lanka
(+94 11) 2695112


dr_koralage@yahoo.co.uk


Primary study sponsor/organization

Yanee Hutagalung, MD
Regional Medical Director (Asia), Vaccines Business Unit
Takeda Vaccines, Inc. One Takeda Parkway Deerfield, IL 60015 U.S.A.
+65 9857-8539

Yanee.Hutagalung@takeda.com

Secondary study sponsor (If any)

None