Takeda announced that it has completed enrollment of 20,100 children and adolescents ages 4 through 16in its global, pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, a double-blind, randomized and placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of its live-attenuated tetravalent dengue vaccine candidate (TAK-003) Takeda initiated the TIDES trial, the largest vaccine clinical trial for Takeda to date, in September 2016 and completed enrollment in less than seven months.
“The successful enrollment of more than 20,000 children and adolescents in this Phase 3 trial, across several continents, and on an ambitious timeline, while maintaining a clear focus on quality and subject safety, reflects Takeda’s prioritization of dengue and the substantial capabilities of our global organization,” said Rajeev Venkayya, MD, President of the Global Vaccine Business Unit at Takeda.
The study is taking place in eight dengue-endemic countries in Latin America and Asia: Brazil, Colombia, Panama, Dominican Republic, Nicaragua, Philippines, Thailand and Sri Lanka. While dengue can affect people of all ages, it is a leading cause of serious illness among children in some countries in Latin America and Asia. The enrollment of children and adolescents between the ages of 4 and 16 years underscores the significant burden of dengue disease across the entire pediatric age range. Initial results of the TIDES trial are expected in 2018.
TIDES will build on previous studies which have assessed the tolerability, safety and immunogenicity of the vaccine against all four dengue serotypes in multiple age groups to determine whether the vaccine helps prevent symptomatic dengue. In Phase 1 and Phase 2 studies, Takeda’s vaccine candidate induced neutralizing antibody responses against all four dengue virus serotypes across age groups and in both seropositive and seronegative individuals with no observed safety concerns. Interim results of one Phase 2 study (DEN-203) showed the vaccine to be generally safe and well tolerated. Results also showed that adults vaccinated with two doses had a sustained immune response against all four serotypes of the dengue virus, even after two years. Interim results of another Phase 2 study (DEN-204) showed an acceptable safety profile in endemic pediatric populations, as well as antibody responses against the four dengue serotypes in dengue seropositive and seronegative participants, with a sustained immune response through 180 days.
“This enrollment milestone demonstrates our commitment to a thorough evaluation of the safety and efficacy of our vaccine candidates and, subject to licensure, ensuring that they are available to all populations at risk. It follows Takeda’s recent decision to invest more than 100 million euros to build a new plant for the manufacturing of TAK-003,” said Venkayya. “Beyond dengue, Takeda is pursuing a number of vaccine programs to address high-priority infectious diseases including our Zika program funded by the U.S. Government’s Biomedical Advanced Research and Development Authority (BARDA) and our polio program supported by the Bill & Melinda Gates Foundation.”
About the Phase 3 TIDES Study
TIDES is investigating the efficacy, safety and immunogenicity of two doses of TAK-003 administered three months apart. TIDES participants were randomized to receive a two-dose regimen of either TAK-003 or placebo by subcutaneous injection at Day 1 and Day 90. A subset of these participants was randomly selected and stratified by region and age to be included in the safety and immunogenicity subsets. Efficacy assessments will take place once 120 cases of virologically confirmed dengue have accrued and after a minimum subject follow-up period of 12 months, post second vaccination.
The primary outcome measure is vaccine protection against virologically-confirmed dengue of any severity, caused by any of the four dengue virus serotypes, regardless of whether a subject has been previously exposed to dengue. Secondary endpoints include vaccine efficacy in preventing dengue induced by each dengue serotype, vaccine efficacy in preventing hospitalization due to dengue induced by any serotype, vaccine efficacy in preventing severe dengue induced by any serotype, frequency and severity of Adverse Events (AEs) or Serious Adverse Events (SAEs), and seropositivity rate and geometric mean titers (GMTs) of neutralizing antibodies in the immunogenicity subset.
Filed Under: Drug Discovery