Clinical Trial: Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II, Double-Blind, Controlled Trial to Assess the Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy

Brief Summary: The purpose of this study is to assess the humoral immune responses to Takeda's Tetravalent Dengue Vaccine Candidate (TDV) administered subcutaneously in a subset of healthy participants between 2 and <18 years of age living in dengue endemic countries.

Detailed Summary:

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to assess how different dosing schedules of the vaccine effect immunity to dengue fever in dengue endemic countries. This study will look at the number of antibodies to dengue fever formed in people who are administered different dosing schedules of TDV.

The study will randomize approximately 1800 patients. Participants will be randomly assigned to one of the four treatment groups in a 1:2:5:1 ratio—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • Group 1 - TDV 0.5 mL subcutaneous (SC) injection Days 1 and 91
  • Group 2 - TDV 0.5 mL SC injection Day 1
  • Group 3 - TDV 0.5 mL SC injection Days 1 and 365
  • Placebo (dummy SC) - this is a liquid that looks like the study drug but has no active ingredient

In order to keep the treatment arms undisclosed to the patient and the doctor, participants will receive a placebo injection at any study visit where TDV is not being administered (Days 91 and/or 365).

Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 28 days after each vaccination.

This multi-centre trial will be conducted in Asia and Latin America. The overall time to participate in this study is up to 18 months. Participants will make 7 visits to the clinic including a final visit 6 months after last dose of study drug for a follow-up assessment.


Sponsor: Takeda

Current Primary Outcome: Geometric Mean Titers (GMTs) of neutralizing antibodies (microneutralization test [MNT50]) for each of the four DENV Serotypes [ Time Frame: Months 1, 3, 6, 12, 13, 18, 24, 36, and 48 ]

The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.


Original Primary Outcome: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four DENV Serotypes [ Time Frame: Months 0, 1, 3, 6, 12, 13 and 18 ]

The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.


Current Secondary Outcome:

  • Seropositivity rates (%) for each of the four DENV serotypes where seropositivity (MNT50) is defined as a reciprocal neutralizing titer ≥ 10 [ Time Frame: Months 1, 3, 6, 12, 13, 18, 24, 36, and 48 ]
    Seropositivity is defined as a reciprocal neutralizing titer ≥ 10.
  • Percentage of Participants with Solicited Local and Systemic Adverse Events (AEs) in the Immunogenicity Subset [ Time Frame: Days 7 and 14 after each vaccination ]
    Solicited local AEs at injection site are defined as pain, erythema and swelling. Solicited systemic AEs in infants/toddlers (15-24 months) and children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite. Solicited systemic AEs in adults and children (≥ 6 years) are defined as fever, asthenia, headache, malaise and myalgia.
  • Severity of Solicited Local and Systemic Adverse Events (AEs) in the Immunogenicity Subset [ Time Frame: Days 7 and 14 after each vaccination ]
    Solicited local AEs are defined as pain, erythema and swelling. Solicited systemic AEs in infants/toddlers (15-24 months) and children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite. Solicited systemic AEs in adults and children (≥ 6 years) are defined as fever, asthenia, headache, malaise and myalgia.
  • Percentage of Participants in the Immunogenicity Subset with Any Unsolicited Adverse Events (AEs) [ Time Frame: Day 28 after each vaccination ]
    Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
  • Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to Day 540 ]
    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.
  • Percentage of Participants with Febrile Episodes of Virologically Confirmed Dengue [ Time Frame: Up to Day 540 ]
    Participants with febrile illness (defined as temperature ≥ 38°C on 2 consecutive days) will be evaluated for dengue. A dengue infection will be considered virologically confirmed by either positive polymerase chain reaction (PCR) or NS1 enzyme-linked immunosorbent assay (ELISA).


Original Secondary Outcome:

  • Percentage of Participants Seropositive to each of the Four DENV Serotypes [ Time Frame: Months 0, 1, 3, 6, 12, 13 and 18 ]
    Seropositivity is defined as a reciprocal neutralizing titer ≥ 10.
  • Percentage of Participants with Solicited Local and Systemic Adverse Events (AEs) in the Immunogenicity Subset [ Time Frame: Days 7 and 14 after each vaccination ]
    Solicited local AEs at injection site are defined as pain, erythema and swelling. Solicited systemic AEs in infants/toddlers (15-24 months) and children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite. Solicited systemic AEs in adults and children (≥ 6 years) are defined as fever, asthenia, headache, malaise and myalgia.
  • Severity of Solicited Local and Systemic Adverse Events (AEs) in the Immunogenicity Subset [ Time Frame: Days 7 and 14 after each vaccination ]
    Solicited local AEs are defined as pain, erythema and swelling. Solicited systemic AEs in infants/toddlers (15-24 months) and children (< 6 years) are defined as fever, irritability/fussiness, drowsiness and loss of appetite. Solicited systemic AEs in adults and children (≥ 6 years) are defined as fever, asthenia, headache, malaise and myalgia.
  • Percentage of Participants in the Immunogenicity Subset with Any Unsolicited Adverse Events (AEs) [ Time Frame: Day 28 after each vaccination ]
    Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
  • Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to Day 540 ]
    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.
  • Percentage of Participants with Febrile Episodes of Virologically Confirmed Dengue [ Time Frame: Up to Day 540 ]
    Participants with febrile illness (defined as temperature ≥ 38°C on 2 consecutive days) will be evaluated for dengue. A dengue infection will be considered virologically confirmed by either positive polymerase chain reaction (PCR) or NS1 enzyme-linked immunosorbent assay (ELISA).


Information By: Takeda

Dates:
Date Received: November 24, 2014
Date Started: December 2014
Date Completion: July 2019
Last Updated: November 24, 2016
Last Verified: November 2016