Description

TAK-003 is an investigational live-attenuated tetravalent dengue vaccine, preventing dengue fever caused by any of the four serotypes of the dengue virus, each of which can cause dengue fever or Severe Dengue. Takeda's tetravalent dengue vaccine candidate TAK-003 (TDV) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses.

Clinical Phase 1 and 2 data in children and adolescents showed that TAK-003 induced immune responses against all four dengue serotypes, in both seropositive and seronegative participants, and the vaccine was found to be generally safe and well-tolerated.

In a November 2019 study, Takeda’s dengue vaccine candidate demonstrated protection against virologically-confirmed dengue, the trial primary endpoint, in children ages 4 to 16 years. The vaccine efficacy (VE) was 80.2% in the 12-month period after the 2nd vaccine dose, which was administered 3-months after the 1st dose.

The TAK-003 vaccine is not currently licensed anywhere in the world. 

Indication

TAK-003 is indicated for the prevention of the Dengue virus caused by any of the 4 Dengue serotypes.

Dosage

TAK-003 will be given as a single DV 0.5 mL subcutaneous injection on Day 1 and Day 90 in the clinical trial. The onset of protection was seen after the 1st dose, with 81% VE between the 1st and 2nd doses.

Updates

November 23, 2019: Takeda presented 18-month data from the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial of its dengue vaccine candidate (TAK-003) at the 68th American Society of Tropical Medicine and Hygiene (ASTMH) taking place in National Harbor, MD from November 20-24.

The trial met all secondary endpoints for which there were a sufficient number of cases, looking at overall vaccine efficacy, as well as secondary efficacy by serotype, baseline serostatus and disease severity including hospitalizations as well as severe dengue. The additional data build upon the 12-month primary efficacy endpoint data published online in the New England Journal of Medicine. Safety and efficacy will continue to be assessed over a total of 4.5 years.

November 6, 2019: Takeda’s Dengue Vaccine Candidate Demonstrates Protection in Children Ages Four to 16 Years, Regardless of Previous Dengue Exposure. The results from this Phase 3 study, Efficacy, Safety, and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TIDES) concluded the Takeda vaccine candidate TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. Results demonstrated overall vaccine efficacy of 80.2% (12-month follow-up after second dose) against virologically confirmed dengue; exploratory analyses of secondary endpoints showed 82.2% vaccine efficacy among baseline seropositives and 74.9% vaccine efficacy among baseline seronegatives.

November 5, 2019 – Takeda Pharmaceutical Company announced the opening of its new manufacturing plant in Singen, Germany, for its dengue vaccine candidate, TAK-003. 

January 29, 2019: Takeda announced TAK-003 which is in a pivotal Phase 3 trial met the primary efficacy endpoint. This first analysis of the Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial showed that the company’s investigational live-attenuated tetravalent dengue vaccine was efficacious in preventing dengue fever caused by any of the 4 serotypes of the virus. While the review of the extensive data set is ongoing, TAK-003 was well tolerated with no significant safety concerns to date. The TIDES trial is continuing and additional results are expected later this year, along with results from other Phase 3 studies.

September 7, 2016 - Takeda Initiates Global Phase 3 Clinical Trial (TIDES) of Dengue Vaccine Candidate (TAK-003).

Clinical Trials

Takeda’s investigational live-attenuated tetravalent dengue vaccine candidate, TAK-003, is being studied in both healthy children and adults, in dengue-endemic and non-endemic countries. Its clinical development program consists of five Phase 3 trials.

Clinical Trial NCT03999996: (NEW) Long-Term Safety and Antibody Persistence of TDV and Impact of a Booster Dose

• This new Phase 3 study will look at the long-term antibody persistence and safety of Takeda's TDV in healthy adolescents and adults and will assess the impact of a booster dose.
• The study will enroll approximately 600 healthy participants. Participants who previously received TDV in two-parent trials (DEN-304 [NCT03423173] and DEN-315 [NCT03341637]), will be invited to participate in this follow-up trial. Participants will be assessed for antibody persistence and safety from Baseline (Month 0) through Month 36. At Month 36, eligible participants will be randomized in 1:1 ratio to one of two trial groups to receive TDV or placebo:
• Group 1- TDV 0.5 mL subcutaneous (SC) injection at Month 36 Group 2- Takeda's tetravalent dengue placebo (dummy SC injection - this is a liquid that looks like the study drug but has no active ingredient), 0.5 mL, subcutaneous injection at Month 36
• This multi-center trial will be conducted in the United States and Mexico. The overall time to participate in this study is up to 42 months. Participants will make 7 visits to the clinic including a final visit 6 months after the last dose of study drug for a follow-up assessment.

Clinical Trial NCT02747927: Efficacy, Safety, and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children (TIDES)

• This Phase III, Double-Blind, Randomized, Placebo-Controlled Trial is to Investigate the Efficacy, Safety and Immunogenicity of a Tetravalent Dengue Vaccine (TDV) Administered Subcutaneously in 21,000 Healthy Children Aged 4 - 16 Years Old
• The purpose of this study is to evaluate the efficacy of 2 doses of Tetravalent Dengue Vaccine Candidate (TDV) in preventing symptomatic dengue fever of any severity, due to any of the four dengue virus serotypes in 4 to 16-year-old participants.
• TAK-003 was efficacious in preventing dengue fever caused by any of the four serotypes of the virus. While the review of the extensive data set is ongoing, TAK-003 was well tolerated with no significant safety concerns to date.
• The Phase 3 clinical trial is continuing and additional results are expected later this year.

Clinical Trial NCT02302066: Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

• TDV is being tested in this Phase 2 study to assess how different dosing schedules of the vaccine effect immunity to dengue fever in dengue-endemic countries. This study will look at the number of antibodies to dengue fever formed in people who are administered different dosing schedules of TDV.
• The study will randomize approximately 1800 patients. Participants will be randomly assigned to one of the four treatment groups in a 1:2:5:1 ratio—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
  • Group 1 - TDV 0.5 mL subcutaneous (SC) injection Days 1 and 91
  • Group 2 - TDV 0.5 mL SC injection Day 1
  • Group 3 - TDV 0.5 mL SC injection Days 1 and 365
  • Placebo (dummy SC) - this is a liquid that looks like the study drug but has no active ingredient
• In order to keep the treatment arms undisclosed to the patient and the doctor, participants will receive a placebo injection at any study visit where TDV is not being administered (Days 91 and/or 365).
• Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 28 days after each vaccination.
• This multi-center trial will be conducted in Asia and Latin America. The overall time to participate in this study is up to 18 months. Participants will make 7 visits to the clinic including a final visit 6 months after the last dose of study drug for a follow-up assessment.

Clinical Trial NCT01765426: Phase 1b Study Investigating Safety & Immunogenicity of TDV Given Intradermally by Needle or Needle-Free PharmaJet Injector

• This is an exploratory trial to assess the safety, tolerability, and immunogenicity of vaccination with a tetravalent dengue vaccine (TDV) in healthy adults delivered intradermally using the conventional needle/syringe or a needle-free PharmaJet® injector.
• Two (2) intradermal injections of either vaccine or placebo will be administered to qualified participants (one in each arm) on Day 0 of the study. A subsequent injection will also be given on Day 90 with either vaccine or placebo (in one arm only).
• Participants will be evaluated for safety and dengue neutralizing antibody to all four serotypes. All participants will also be evaluated for injection site reactions and have blood drawn for viremia, neutralizing antibodies, cell-mediated immunity and innate immunity.
• Participants will be required to participate for approximately 10 months from recruitment and collection of data for primary outcomes (through Day 120) including the collection of additional samples for measurement of longer-term antibody titers (through Day 270).
• This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201000034C.