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Takeda's Tetravalent Dengue Vaccine Candidate

Phase 2

Dengue Fever | Monoclonal antibody | Infectious Disease |Takeda Pharmaceutical Company Limited|Last Updated: Feb 24, 2020

Target and mechanism

ModalityMonoclonal antibody

Also known as Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment2,151

FDA Designations

No designations recorded

Clinical trial landscape

Takeda's Tetravalent Dengue Vaccine Candidate · 3 trials · 2 indications

Phase 2 2Phase 1 1
NCT02425098Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in SingaporeDengue Fever
COMPLETED351 Analytics
NCT02302066Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy ParticipantsDengue Fever
COMPLETED1,800 Analytics
PHASE2COMPLETED
Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in Singapore
Dengue FeverUnlock trial analytics
PHASE2COMPLETED
Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants
Dengue FeverUnlock trial analytics

Study Endpoints

Primary Endpoints

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15
Day 15

GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test \[MNT\].

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30
Day 30

GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90
Day 90

GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180
Day 180

GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365
Day 365

GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15
Day 15

Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30
Day 30

Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90
Day 90

Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180
Day 180

Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365
Day 365

Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

Geometric Mean Titers (GMTs) of Neutralizing Antibodies (Microneutralization Test [MNT50]) for Each of the Four DENV Serotypes for Participants in the Immunogenicity Subset
Up to Month 48

GMTs of neutralizing antibodies were measured by microneutralization test 50% \[MNT50\] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Data reported for up to Month 48 was collected at Months 1, 3, 6, 12, 13, 18, 24, 36 and 48.

Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported
Day 0 to Day 104

Erythema and Edema Were Graded Per The FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Where Grade 0=none to Grade 4=Severe. Pain and Itching were graded using Common Terminology Criteria for Adverse Events (CTCAE) 4.03 where Grade 0=no pain or itching to Grade 4= Life-threatening/severe. Only those score categories for which there was at least 1 participant are reported.

Number of Participants With at Least 1 Adverse Event Following Either Vaccine Dose
For 30 days after each dose (Up to Day 120)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.

Number of Participants With at Least 1 Adverse Events Related to TDV Following Either Vaccine Dose
For 30 days after each dose (Up to Day 120)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. Some AEs are automatically considered related because of temporal relationship to vaccination.

Rate of Seroconversion to Each of Four Dengue Serotypes
Up to 30 days after the last immunization (Up to Day 120)

Rate of seroconversion was defined as the percentage of participants with Plaque Reduction Neutralization Test titer resulting in 50 % reduction in Plagues (PRNT50) titer ≥ 10 for participants seronegative at Baseline or a greater than four-fold increase in PRNT50 for participants seropositive at Baseline.

Secondary Endpoints

Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Within 7 days after Vaccination
Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity
Within 14 days after Vaccination
Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination
Within 28 days after Vaccination
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposePREVENTION

Treatment Arms

ArmTypeDescription
High-dose Tetravalent Dengue Vaccine (HD-TDV)EXPERIMENTALHigh-dose Tetravalent Dengue Vaccine \[HD-TDV\], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2\*10\^4 plaque forming units (PFU), 5\*10\^4 PFU, 1\*10\^5 PFU, and 3\*10\^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.
Tetravalent Dengue Vaccine (TDV)EXPERIMENTALTetravalent Dengue Vaccine \[TDV\], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2\*10\^4 plaque forming units (PFU), 5\*10\^3 PFU, 1\*10\^5 PFU, and 3\*10\^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.
Group 1 (TDV 2-Dose)EXPERIMENTALTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 91. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 365.
Group 2 (TDV 1-Dose)EXPERIMENTALTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Day 1. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 91 and 365.
Group 3 (TDV 1-Dose + Booster)EXPERIMENTALTakeda's tetravalent dengue vaccine candidate (TDV), 0.5 mL, subcutaneous injection on Days 1 and 365. Placebo-matching vaccine, 0.5 mL, subcutaneous injection on Day 91.
Group 4 (Placebo Control)PLACEBO_COMPARATORPlacebo-matching vaccine, 0.5 mL, subcutaneous injection on Days 1, 91 and 365.
Group 1EXPERIMENTALTakeda's Tetravalent Dengue Vaccine Candidate (TDV), 0.5 mL, subcutaneous injection in one arm and placebo, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.
Group 2EXPERIMENTALTDV, 0.5 mL, subcutaneous injection in one arm and TDV 0.5 mL, subcutaneous injection in the other arm on Day 0. Placebo, 0.5 mL, subcutaneous injection on Day 90.
Group 3EXPERIMENTALTDV, 0.5 mL, subcutaneous injection in one arm and TDV, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.
Group 4EXPERIMENTALTDV new formulation, 0.5 mL, subcutaneous injection in one arm and new formulation placebo, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.
Group 5EXPERIMENTALTDV new formulation, 0.5 mL, subcutaneous injection in one arm and TDV new formulation, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.
Group 6EXPERIMENTAL1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.

Interventions

NameTypeDescription
Takeda's Tetravalent Dengue Vaccine Candidate (TDV)BIOLOGICALTDV subcutaneous injection
Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)BIOLOGICALHigh-dose TDV subcutaneous injection
TDV PlaceboBIOLOGICALPlacebo-matching vaccine
TDV New FormulationBIOLOGICALTDV New Formulation subcutaneous injection
PlaceboDRUGPlacebo subcutaneous injection
New Formulation PlaceboDRUGNew Formulation placebo subcutaneous injection
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Eligibility Criteria

Age Range21 Years to 45 Years
SexALL
Healthy VolunteersYes
Study Sites3

Inclusion Criteria: 1. Participant signs and dates a written informed consent form where applicable, and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements. 2. Is aged 21 to ...

Countries:SingaporeDominican RepublicPanamaPhilippinesUnited States
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