Date

2021-03-30

Protocol

Protocol changed

Item Changed

Intervention(s) planned

Previous Version

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.

Next Version

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. although a generally consistent overall efficacy and continued protection against hospitalized dengue is observed after a 2-dose vaccination regimen with TDV (2 single doses 3 months apart), data also indicate a trend towards a reduction in overall vaccine efficacy in the second year after vaccination. This observation suggests a waning in vaccine efficacy and therefore the present ongoing phase III trial will evaluate the effect of a booster dose. Due to the absence of a correlate of protection in dengue, the booster effect can only be demonstrated by efficacy data. Adding a booster phase to the present ongoing DEN-301 trial gives the opportunity to administer a booster dose of TDV to assess vaccine efficacy against virologically confirmed dengue The booster phase of this phase III trial is comprised of 2 parts (Parts 4 and 5). Parts 4 and 5 will assess vaccine efficacy (VE) of a booster dose of TDV against symptomatic dengue illness due to any serotype and will provide data on the effect of a booster dose on VE after a 2-dose vaccination regimen with TDV (2 single doses 3 months apart). Subjects will receive a single dose of TDV or placebo, depending on the assignment at the time of randomization in the trial (Day 1 [Month 0]). The trial blind will be maintained. No new randomization will be performed for the booster phase of the trial. Only subjects from the Per-Protocol Set (PPS) who were 4 to 11 years of age at the time of randomization in the trial (Day 1 [Month 0]) will receive the booster vaccination between 4 years and approximately 4.5 years post-dose 2 vaccination regimen. Additional informed consent/assent must be obtained prior to the subject entering into the booster phase of the trial, and before any protocol-directed procedures are performed for the booster phase. Subjects will keep the same unique identification number assigned at the time of trial entry. Subjects who would become of legal age (18 years of age in all participating countries) during the booster phase of the trial will be asked to provide informed consent as legal adults, ideally within approximately 3 weeks after the 18th birthday, to remain in the trial.