The Lancet publishes papers from two studies of Takeda’s dengue vaccine candidate
- Results published in first paper from 18-month analysis of ongoing pivotal Phase 3 trial were generally consistent with overall efficacy and safety data reported in previously published 12-month analysis.
- Pivotal Phase 3 trial met all secondary endpoints for which there were a sufficient number of dengue cases.
- In the second paper, final 48-month results from a Phase 2 trial described long-term safety and demonstrated the durability of immune responses to Takeda’s dengue vaccine candidate. Results further support the two-dose schedule studied in pivotal Phase 3 trial.
The 18-month data analysis from the pivotal Phase 3 TIDES trial includes an update on overall vaccine efficacy (VE) and a formal assessment of secondary efficacy endpoints by serotype, baseline serostatus and disease severity (18 months after the second dose, which was administered three months after the first dose), demonstrating protection against virologically confirmed dengue (VCD) in children ages four to 16 years (overall VE was 73.3% [95% confidence interval (CI): 66.5% to 78.8%]. The TIDES trial met all secondary endpoints for which there were a sufficient number of dengue cases. TAK-003 was generally well tolerated, and there were no important safety risks identified within this analysis.1 The 18-month data were previously presented at the
“I see first-hand the devastation that dengue can bring to communities and individuals and the pressure it puts on healthcare systems. There is a great need for a vaccine that is safe and effective in reducing not only the incidence and severity of disease but also the hospitalization rate,” said
The TIDES trial is continuing, and safety and efficacy will be assessed over a total of four and a half years.
The DEN-204 study enrolled 1,800 participants. In the 48-month data analysis, TAK-003 was shown to elicit antibody responses against all four dengue serotypes in children and adolescents ages two to 17 years, which persisted through four years post-vaccination, regardless of baseline serostatus. Three different dose schedules (one primary dose; one primary dose plus one-year booster dose; or two-dose primary series), and placebo were assessed. In baseline seropositive participants, no clear differences in geometric mean titers (GMTs) – an indication of immune response – were shown between the dosing schedules by Month 48. In the baseline seronegative participants, GMTs were generally lower against all four serotypes in those who received one dose compared with either the two-dose primary series or the one dose plus one-year booster series, further supporting the use of the two-dose primary series studied in the ongoing TIDES trial. No important safety risks were identified throughout the four-year study period, providing insight into the long-term safety profile of TAK-003. While VE was not assessed in this study, there was a significantly lower risk of VCD in the vaccine groups compared with placebo over the four-year study period (relative risk: 0.35; 95% CI: 0.19-0.65).2 Results of previous interim analyses of the DEN-204 study demonstrated persistence of immunogenicity along with tolerability and safety assessments at six5 and 18 months.6
“Dengue threatens families and communities around the globe, and there remains a critical need for a vaccine that is safe in all people regardless of previous dengue exposure,” said
About the Phase 3 TIDES (DEN-301) Trial
The double-blind, randomized, placebo-controlled Phase 3 TIDES trial is evaluating the safety and efficacy of two doses of TAK-003 in the prevention of laboratory-confirmed symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in children and adolescents.7 The TIDES trial is Takeda’s largest interventional clinical trial to date and enrolled over 20,000 healthy children and adolescents ages four to 16 years living in dengue-endemic areas. Study participants were randomly assigned to receive either TAK-003 0.5 mL or placebo by subcutaneous injection on Day 1 and Day 90.7 The study is comprised of three parts. The primary endpoint analysis evaluated vaccine efficacy (VE) and safety through 15 months after the first dose (12 months after the second dose).7 The second part of the study continued for an additional six months to complete the assessment of the secondary endpoints of VE by serotype, baseline serostatus and disease severity.7 The final part of the study is evaluating VE and long-term safety by following participants for an additional three years.7
The trial is taking place at sites in dengue-endemic areas in
About the Phase 2 DEN-204 Trial
The Phase 2 DEN-204 study was a randomized, double-blind, placebo-controlled, multi-center trial designed to assess the safety and immunogenicity of either a one- or two-dose schedule of TAK-003 in 1,794 healthy participants living in dengue-endemic areas (the
Dengue is the fastest spreading mosquito-borne viral disease and is one of the World Health Organization’s top 10 threats to global health in 2019.13,14 Dengue is mainly spread by Aedes aegypti mosquitoes and, to a lesser extent, Aedes albopictus mosquitoes. It is caused by any of four dengue virus serotypes, each of which can cause dengue fever or severe dengue.13 The prevalence of individual serotypes varies across different geographies, countries, regions, seasons and over time.13,15 Recovery from infection by one serotype provides lifelong immunity against only that serotype, and later exposure to any of the remaining serotypes is associated with an increased risk of severe disease.13
Dengue is pandemic prone, and outbreaks are observed in tropical and sub-tropical areas and have recently caused outbreaks in parts of the continental
Takeda’s Commitment to Vaccines
Vaccines prevent 2 to 3 million deaths each year and have transformed global public health.19 For the past 70 years,
For more information, visit https://www.takeda.com.
1 Biswal S, et al. Efficacy of a tetravalent dengue vaccine in health children aged 4-16 years: a randomized, placebo-controlled, phase 3 trial.
2 Tricou, V, Sáez-Llorens X, et al. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2-17 years: a randomised, placebo-controlled, phase 2 trial.
3 Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 2019;381:2009-2019.
4 Biswal S. Efficacy of a tetravalent dengue vaccine in healthy 4 to 16-year-old children. Presented at 68th Annual Meeting,
5 Sáez-Llorens X, Tricou V, et al. Safety and immunogenicity of one versus two doses of
6 Sáez-Llorens X, Tricou V, et al. Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2–17 years in
7ClinicalTrials.gov. Efficacy, Safety and Immunogenicity of
8ClinicalTrials.gov. Safety and Immunogenicity of Different Schedules of
9 Huang CY-H, et al. Genetic and phenotypic characterization of manufacturing seeds for tetravalent dengue vaccine (DENVax). PLoS Negl Trop Dis. 2013;7:e2243.
10 Osorio, JE, et al. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in
11 Wallace D. Persistence of neutralizing antibodies one year after two doses of a candidate recombinant tetravalent dengue vaccine in subjects aged from 1.5 to 45 years. Presented at 64th Annual Meeting,
15 Guzman MG, et al. Dengue: a continuing global threat. Nature Reviews Microbiology. 2010;8:S7-S16.
16 Knowlton K, et al. Mosquito-Borne Dengue Fever Threat Spreading in the
17 Chan E, et al. Using web search query data to monitor dengue epidemics: a new model for neglected tropical disease surveillance. PLoS Negl Trop Dis. 2011;5:e1206..