Clinical trial NCT02948829: Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children
Official title: An Open Label, Phase 2 Study to Investigate Cell-mediated Immunity and Safety of a Tetravalent Dengue Vaccine Candidate (TDV) Administered Subcutaneously in Healthy Children Aged 4 to 16 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteers
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-10-28
Enrollment: 200
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the cellular immune responses following 2 doses given 3 months apart of tetravalent dengue vaccine candidate (TDV) in 4 to 16 years' healthy participants.

Detailed description: The vaccine tested in this study was TDV. This study assessed cellular immune responses and safety up to 3 years post second TDV administration to healthy children aged 4 to 16 years and in dengue endemic regions.

The study enrolled 200 participants. Participants received:

• TDV 0.5 mL subcutaneous (SC) injection into the upper arm at Day 1 (Month 0) and at Day 90 (Month 3).

This multi-center trial was conducted in Panama and Philippines. 198 participants received the 2-dose schedule of TDV, and 2 participants received only the first dose of TDV (Day 1). Participants made multiple visits to the clinic and were contacted at least every week for the entire study duration post first injection.

Eligibility criteria: Main Inclusion Criteria:

1. Is aged 4 to 16 years, inclusive (Latin America) or 4 to 8 years, inclusive (Asia).
2. Are in good health at the time of entry into the study as determined by medical history, physical examination (including vital signs), and clinical judgment of the investigator.

Main Exclusion Criteria:

1. Febrile illness (body temperature ≥38°C) or moderate or severe acute illness or infection at the time of enrolment.
2. History or any illness that, in the opinion of the investigator, might interfere with the results of the study or pose an additional risk to the participant due to participation in the study.
3. Receipt of any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccines within 28 days after Day 1 (Month 0).
4. Previous participation in any clinical study of a dengue candidate vaccine, or previous receipt of any dengue vaccines (investigational or licensed).

Primary outcomes:
measure: Percentage of Participants With Cellular Immune Response to 2 Doses of Tetravalent Dengue Vaccine (TDV) at 1 Month Post Second Vaccination
timeFrame: 1 month post second vaccination (Day 120)
Secondary outcomes:
measure: Magnitude of Cellular Immune Response Assessed by Number of Spot Forming Cells (SFC)/Million Peripheral Blood Mononuclear Cells (PBMCs) Measured by IFN-γ ELISPOT at 1 Month Post Second Vaccination
timeFrame: 1 month post second vaccination (Day 120)
measure: Percentage of Participants With Cellular Immune Response to TDV at 1 Month Post First Vaccination, Pre-second Vaccination, 6 Months Post Second Vaccination, and Annually at Years 1, 2, and 3
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 6 months post second vaccination (Day 270); Years 1, 2 and 3
measure: Magnitude of Cellular Immune Response Assessed by Number of SFC/Million PBMCs Measured by IFN-γ ELISPOT at 1 Month Post First Vaccination, Pre-second Vaccination, 6 Months Post Second Vaccination, and Annually at Years 1, 2, and 3
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 6 months post second vaccination (Days 120 and 270); Years 1, 2 and 3
measure: Percentage of Participants With Cellular Immune Responses to TDV at 1 Month Post First Vaccination, Pre-second Vaccination, 1 and 6 Months Post Second Vaccination, and Annually at Years 1, 2, and 3 Assessed by Country
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90) 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, 3
measure: Percentage of Participants With Cellular Immune Responses to TDV:1 Month Post First Vaccination, Pre-second Vaccination, 1 and 6 Months Post Second Vaccination, and Annually at Years 1, 2, and 3, by Dengue Baseline Seropositivity Status
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Magnitude of Cellular Immune Response Assessed by Number of SFC/Million PBMCs Measured by IFN-γ ELISPOT at 1 Month Post First, Pre- Second Vaccination, 1 and 6 Months Post Second Vaccination, and Annually at Years 1, 2, and 3 by Country
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Magnitude of Cellular Immune Response Assessed by Number of SFC/Million PBMCs Measured by IFN-γ ELISPOT 1Month Post First Vaccination,Pre-second Vaccination;1,6Months Post Second Vaccination, Annually at Years1,2,3 by Dengue Baseline Seropositivity Status
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Percentage of Participants With Cellular Immune Response to TDV in Participants >10 Years of Age
timeFrame: Day 14
measure: Magnitude of Cellular Immune Response Assessed by Number of SFC/Million PBMCs Measured by IFN-γ ELISPOT in Participants >10 Years of Age
timeFrame: Day 14
measure: Phenotype Characterization of Cellular Immune Response Assessed by Percentage of Total T Cells of Cellular Response to DENV-2 NS Peptides at 1Month Post First Vaccination,Pre-second Vaccination;1,6Months Post Second Vaccination, Annually at Years1,2,3
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Phenotype Characterization of Cellular Immune Response Assessed by Percentage of Total T Cells of Cellular Response DENV-2 NS Peptides,1Month Post First Vaccination,Pre Second Vaccination;1,6Months Post Second Vaccination,Annually at Years1,2,3 by Country
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Phenotype Characterization of Cellular Immune Response by Percentage of Total T Cells DENV-2 NS Peptides at 1Month Post First Vaccination,Pre Second Vaccination;1,6Months Post Second Vaccination,Annually at Years1,2,3 by Dengue Baseline Seropositivity
timeFrame: 1 month post first vaccination (Day 30); pre-second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); Years 1, 2, and 3
measure: Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post First Vaccination, Pre Second Vaccination, and 1, 6 Months Post Second Vaccination and Then Annually Up to 3 Years
timeFrame: 1 month post first vaccination (Day 30); pre second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); annually up to 3 years (Years 1, 2 and 3)
measure: Percentage of Participants Seropositive for Each of the 4 Dengue Serotypes at 1 Month Post First Vaccination, Pre-second Vaccination, and 1, 6 Months Post Second Vaccination and Then Annually up to 3 Years
timeFrame: 1 month post first vaccination (Day 30); pre second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); annually up to 3 years (Years 1, 2 and 3)
measure: Percentage of Participants Seropositive for Multiple Dengue Serotypes at 1 Month Post First Vaccination, Pre Second Vaccination, 1, 6 Months Post Second Vaccination and Annually up to 3 Years
timeFrame: 1 month post first vaccination (Day 30); pre second vaccination (Day 90); 1 and 6 months post second vaccination (Days 120 and 270); annually up to 3 years (Years 1, 2 and 3)
measure: Percentage of Participants Experiencing Unsolicited Adverse Events (AE)
timeFrame: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose on Day 1 [Month 0] and Day 90 [Month 3]
measure: Percentage of Participants With Medically Attended AEs (MAAEs)
timeFrame: From first vaccination (Day 1) up to 6 months post second vaccination (Day 270)
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination (Day 1) up to end of study (Approximately 3 years)
measure: Percentage of Participants With Virologically Confirmed Dengue
timeFrame: From first vaccination (Day 1) up to 6 months post second vaccination (Day 270)
Other outcomes:
Locations:
city: Panama
country: Panama
facility: CEVAXIN
city: Muntinlupa
country: Philippines
facility: Research Institute for Tropical Medicine
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: