AsianScientist (Apr. 5, 2017) – In a study published The Lancet Infectious Diseases, Takeda Pharmaceutical Company Limited has released data from their six-month interim analysis of the the ongoing DEN-204 trial of its live-attenuated tetravalent dengue vaccine candidate, TAK-003 (also referred to as TDV).
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.
Dengue fever is a painful, debilitating mosquito-borne disease caused by any one of four closely related virus serotypes. Forty percent of the world lives under the threat of dengue, which can affect people of all ages and is a leading cause of serious illness and death among children throughout the world.
“Infection with one dengue serotype makes subsequent infection with a different serotype a major risk factor for severe disease, hence the need for a safe and effective vaccine that simultaneously protects against all four serotypes,” said Dr. Xavier Sáez-Llorens, primary author of study and Head of Infectious Diseases and Director of Clinical Research at the Panama Children’s Hospital.
The published data showed that TAK-003 elicited a broad antibody response against all four dengue virus serotypes, regardless of previous exposure to the dengue virus. The increased presence of antibodies in the blood against the four serotypes ranged between 87-100 percent by month 1 and was sustained at month 6 (85-100 percent), in both the one-dose and two-dose groups.
The analysis also showed that, in participants who were not previously exposed to dengue infection 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.
“The levels of immunogenicity induced by TAK-003 against all four dengue serotypes, even in seronegative participants, are encouraging because seropositivity after vaccination may be an important measure of vaccine performance,” Sáez-Llorens said.
“The durability of these antibody responses and the contribution of cell-mediated immune responses to disease protection warrant further study.”
The 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 was limited.
“These and other Phase 1 and Phase 2 safety and immunogenicity data support continued development of this important vaccine candidate,” said Dr. Derek Wallace, Global Dengue Program Head at Takeda. “We look forward to ongoing studies, which will assess the candidate vaccine’s ability to provide protection against all four dengue serotypes in recipients of all ages, whether or not they have been previously exposed to dengue.”
In September 2016, Takeda initiated its pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES). The randomized, double-blind, placebo-controlled, multi-center trial is designed to investigate the efficacy, safety and immunogenicity of Takeda’s dengue vaccine candidate, administered in two doses, three months apart, in dengue-endemic countries in Latin America and Asia.
Evaluation of the trial’s primary endpoint, vaccine protection against virologically-confirmed dengue of any severity caused by any serotype regardless of previous exposure, is expected in 2018. Secondary endpoints include vaccine efficacy in preventing dengue induced by each serotype, vaccine efficacy in preventing dengue caused by any serotype regardless of participants’ baseline status, vaccine efficacy in preventing hospitalization due to dengue, and vaccine efficacy in preventing severe dengue induced by any serotype.
The article can be found at: Sáez-Llorens et al. (2017) 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.
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Source: Takeda; Photo: Shutterstock.
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