Date: 2017-03-30
Type of
information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in The Lancet Infectious Diseases
Company: Takeda Pharmaceutical (Japan)
Product: TAK-003 (live-attenuated tetravalent dengue vaccine candidate)
Action
mechanism:
- vaccine. TAK-003 is a tetravalent dengue vaccine candidate based on a live-attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘backbone’ for all four vaccine viruses. Phase 1 data has been published in the Journal of Infectious Diseases, Lancet Infectious Diseases, and Vaccine. Interim results of DEN-203, a Phase 2, placebo-controlled, multi-center, age-descending trial, were presented during the American Society of Tropical Medicine and Hygiene (ASTMH) meeting in October 2015. Interim results of DEN-204, a Phase 2, placebo-controlled, multi-center trial were presented during the 5th Annual Pan-American Dengue Research Network Meeting in May 2016.
Disease: dengue fever
Therapeutic
area: Infectious diseases
Country: Dominican Republic, Panama, the Philippines
Trial
details:
- The Phase 2 DEN-204 study is 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 Dominican Republic, Panama and the Philippines). Participants were ages two through 17 and were randomized to one of four groups, two of which received a one-dose vaccine schedule, one of which received a two-dose vaccine schedule administered three months apart, and one which received placebo, by the 6 month interim analysis timepoint.
- The primary endpoint of this interim analysis was geometric mean titers (GMTs) of neutralizing antibodies (an indicator of immune response) to the four dengue virus serotypes (DENV-1-4) in the per protocol immunogenicity subset (PPS), a group of participants who had no major protocol violations and for whom valid pre- and post-dosing blood samples were available and immunogenicity was evaluated, at months one, three, and six.
- Secondary endpoints included occurrence of serious adverse events, seropositivity rates (percentage of participants who developed antibodies), and adverse events in the immunogenicity subset.
Latest
news:
- • On March 30, 2017, Takeda Pharmaceutical announced that data from a 6-month interim analysis of the ongoing DEN-204 trial of its live attenuated tetravalent dengue vaccine candidate, TAK-003 (also referred to as TDV), have been published in The Lancet Infectious Diseases (Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study. Prof Xavier Sáez-Llorens et al).
- The trial investigated the safety and immunogenicity of TAK-003 in 1,794 participants ages two through 17 living in dengue-endemic areas (the Dominican Republic, Panama and the Philippines). At the time of the analysis, participants had either received one dose of TAK-003, two doses of TAK-003 administered three months apart, or a placebo.
- The published data showed that TAK-003 elicited a broad antibody response against all four dengue virus types, regardless of previous exposure to the dengue virus. The increased presence of antibodies in the blood against the four serotypes ranged between 87-100% by Month 1 and was sustained at Month 6 (85-100%), in both the one-dose and two-dose groups.1This analysis also showed that, in participants who were not previously exposed to dengue infection (seronegative) before vaccination, seropositivity rates against dengue virus types 3 and 4 were improved after a second dose of vaccine. For this reason, a two-dose regimen, administered three months apart, was selected for Takeda’s ongoing global pivotal Phase 3 efficacy trial.
- This analysis also showed that TAK-003 was safe and well-tolerated in children and adolescents in terms of solicited local reactions and systemic adverse events; no vaccine-related serious adverse events occurred, and the expected immunological responses to the vaccine and associated signs and symptoms (reactogenicity) was limited. The number of adverse events reported were similar or lower than those reported for other live attenuated vaccines, and the safety profile was consistent with that observed in earlier Phase 1 and 2 studies of the vaccine candidate.
- A pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) is currently ongoing.
Is
general: Yes
