HealthyPhase 2NCT01511250
Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years
A Phase 2 study testing TDV in people with Healthy, run by Takeda at 8 sites in 4 countries.
Trial summary
The purpose of this study is to assess the safety of Takeda's tetravalent dengue vaccine (TDV) (previously DENVax) administered subcutaneously in healthy adults and children. In addition the antibody response to the four dengue virus serotypes will be evaluated. Read more about this study
- Who is it for?
- Ages 18 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- TDV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 360 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 16 Nov 2011to 15 Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- In good health as determined by medical history, physical examination including height and weight
- Normal safety laboratory values at screening
- Negative for human immunodeficiency virus-1 (HIV-1) antibodies, Hepatitis C antibodies \& Hepatitis B surface antigen
- Females negative by urine pregnancy test at screening and immediately prior to injection, and were willing to use reliable means of contraception
- Weight: Within 1.3 times of the upper limit of local normal age-adjusted body mass index (BMI)
Who cannot join
- For participants ≥12 years, clinically significant electrocardiogram (ECG) findings
- History of significant dermatologic (skin) disease within last 6 months
- History of diabetes mellitus
- History of thymic pathology, thymectomy, myasthenia or any immunodeficiency
- History of recurring headaches or migraines
- Hypersensitivity to any vaccine
Show all 9Show fewer
- For participants ≥12 years, positive urine screen for cocaine, amphetamines, opiates, or cannabinoids
- History of alcohol abuse
- Pregnant or lactating female
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Puerto Rico3 sites
Ponce School of Medicine, CAIMED Center
Ponce, 716
University of Puerto Rico School of Medicine
San Juan, 00935
Latin Clinical Trial Center
San Juan, 909
Singapore2 sites
National University Hospital
Singapore, 119228
Changi General Hospital
Singapore, 529889
Thailand2 sites
Faculty of Tropical Medicine, Mahidol University
Bangkok, Bangkok, 10270
Phramongkutklao Hospital
Bangkok, Bangkok, 10400
Colombia1 site
Program For The Study and Control of Tropical Diseases
Medellín
About this study
Official title: A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years
The purpose of this study is to assess the safety of Takeda's tetravalent dengue vaccine (TDV) (previously DENVax) administered subcutaneously in healthy adults and children. In addition the antibody response to the four dengue virus serotypes will be evaluated.
Read the detailed description
The vaccine tested in this study was tetravalent dengue vaccine (TDV). TDV was tested to assess safety and immunogenicity in healthy adults and children living in dengue endemic countries.
The study enrolled 360 healthy participants. The study was conducted in 2 parts, Part 1 - age descending and and Part 2 - expansion - ages 1.5-11 years. Participants were allocated to one of the four age cohorts in Part 1 (21 to 45 years, 12 to 20 years, 6 to 11 years, and 1.5 to 5 years) and expansion age cohort 1.5-11 years in Part 2. Participants were randomized in 2:1 ratio and in 3: 1 ratio in Part 1 and 2 respectively to receive:
- TDV 0.5 mL SC injection
- Placebo (inactive solution) - this is a solution that looks like the study drug but has no active ingredient
This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 37 months (including screening period). Participants made multiple visits to the clinic including a final visit at Day 1080.
- Conditions
- Healthy
- Being tested
- TDV, Placebo
- Keywords
- Normal healthy adults and children, Safety and tolerability, Active vaccine, Placebo, Dengue virus vaccine, Immune response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDVBiological
TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.
PlaceboBiological
TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).
| Study group | Role | What they receive |
|---|---|---|
| Part I: TDV 21 to 45 Years (yrs) | Experimental | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 plaque forming units (PFU), 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. Receives: Biological: TDV |
| Part I: Placebo 21 to 45 yrs | Placebo comparator | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Receives: Biological: Placebo |
| Part I: TDV 12 to 20 yrs | Experimental | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. Receives: Biological: TDV |
| Part I: Placebo 12 to 20 yrs | Placebo comparator | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Receives: Biological: Placebo |
| Part I: TDV 6 to 11 yrs | Experimental | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. Receives: Biological: TDV |
| Part I: Placebo 6 to 11 yrs | Placebo comparator | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Receives: Biological: Placebo |
| Part I: TDV 1.5 to 5 yrs | Experimental | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. Receives: Biological: TDV |
| Part I: Placebo 1.5 to 5 yrs | Placebo comparator | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Receives: Biological: Placebo |
| Part II: TDV 1.5 to 11 yrs | Experimental | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. Receives: Biological: TDV |
| Part II: Placebo 1.5 to 11 yrs | Placebo comparator | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain [Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)] and itching (pruritus) [Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: >10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).
Measured: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity
Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain [Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)] and itching (pruritus) [Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: >10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).
Measured: Within 28 days after either of the vaccination given on Day 0 or 90 (Day 28 for first vaccination, Day 118 for second vaccination)
Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
Solicited systemic AEs (headache, muscle pain [myalgia], joint pain [arthralgia], eye pain, sensitivity to light [photophobia], tiredness [fatigue], body rash, nausea, were recorded in the participant's-diary along with vomiting [number of times]), and body temperature). Diary-recorded severity grades were based on the Common Terminology Criteria for Adverse Events (CTCAE). Severity grades were: Mild (Grade 1): transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities. The CTCAE severity grades for fever and vomiting were derived from the diary-recorded measurements of temperature level and number of episodes, respectively.
Measured: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Number of Participants With Any Solicited AE Following Either Vaccination Dose
An 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. Solicited local injection site reactions included pain, itching, erythema, edema and solicited systemic AEs include myalgia, arthralgia, eye pain, photophobia, fatigue, body rash, nausea, vomiting, and fever.
Measured: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity
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. The severity of all unsolicited AEs was evaluated by the Investigator (using the Common Terminology Criteria for Adverse Events [CTCAE] v4.03) as follows. Mild (Grade 1): Transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): Marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities.
Measured: Unsolicited AEs were collected within 28 days of all vaccinations. Serious AEs were collected throughout the study up to Day 1080
Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120
Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralizing antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 for any serotype and seronegative was defined as titre value of less than (<) 10 for all 4 serotypes. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4.
Measured: 30 days after second vaccination (Day 120)
Secondary outcomes (8)
Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination
Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4 for Part-1. Vaccine viral ribonucleic acid (RNA) was detected by a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.
Measured: Days 0, 7, 14, 90, 97, and 104
Part I: Duration of Vaccine Viremia
Measured: Days 0, 7, 14, 90, 97, and 104
Part I: Titers of Vaccine Viremia
Measured: Days 0, 7, 14, 90, 97, and 104
Seropositivity Rate to Each of the Four Dengue Serotypes
Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralizing antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 and seronegative was defined as titre value of less than (<) 10. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4.
Measured: Day 28 and Day 90 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Seroconversion Rate to Each of the Four Dengue Serotypes
Seroconversion rate was defined as the percentage of participants with microneutralization test 50% (MNT50) titer ≥10 or, if the titer on Day 0 was ≥10, a 4-fold rise in antibody titer.
Measured: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
GMTs were assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, and TDV-4.
Measured: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Geometric Mean Fold Rise (GMFR) of Dengue Neutralizing Antibody Titers for Each of the 4 Dengue Serotypes
Measured: Day 28 and Day 90 (Parts 1 and 2) and Days 120, 180, 360, 720 and 1080 in Part 1
Number of Participants With Confirmed Dengue Fever
Dengue fever was assessed in participants who had 3 consecutive days of fever >38°C and tested positive for dengue virus by polymerase chain reaction (PCR) analysis.
Measured: Day 1 to Day 1080
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2012 (estimated)
- Study start16 Nov 2011
- Primary completion1 Apr 2016
- Study completion15 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511250
- Sponsor's protocol ID
- INV-DEN-203
- Other IDs
- 2022-003455-33
- Status last verified
- Apr 2023
- First submitted
- 16 Nov 2011
- Last updated
- 12 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gottardo R, Dean H, Nascimento EJM, Tricou V, Sharma M. Beyond neutralization: A comprehensive framework for evaluating humoral immunity induced by a live-attenuated tetravalent dengue vaccine. Vaccine. 2026 Aug 13;88:128929. doi: 10.1016/j.vaccine.2026.128929. Epub 2026 Jul 21.
PubMed 42480195Rauscher M, Youard Z, Faccin A, Patel SS, Pang H, Zent O. Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine. Expert Rev Vaccines. 2025 Dec;24(1):221-229. doi: 10.1080/14760584.2025.2480297. Epub 2025 Mar 27.
PubMed 40099800Nascimento EJM, Norwood B, Kpamegan E, Parker A, Fernandes J, Perez-Guzman E, Tricou V, Braun R, Sharma M, Dean HJ. Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System. J Infect Dis. 2023 May 29;227(11):1282-1292. doi: 10.1093/infdis/jiac476.
PubMed 36461942Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
PubMed 33534885Sirivichayakul C, Barranco-Santana EA, Rivera IE, Kilbury J, Raanan M, Borkowski A, Papadimitriou A, Wallace D. Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study. J Infect Dis. 2022 May 4;225(9):1513-1520. doi: 10.1093/infdis/jiaa406.
PubMed 32658250Sharma M, Glasner DR, Watkins H, Puerta-Guardo H, Kassa Y, Egan MA, Dean H, Harris E. Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate. J Infect Dis. 2020 Mar 2;221(6):867-877. doi: 10.1093/infdis/jiz081.
PubMed 30783676Rupp R, Luckasen GJ, Kirstein JL, Osorio JE, Santangelo JD, Raanan M, Smith MK, Wallace D, Gordon GS, Stinchcomb DT. Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study. Vaccine. 2015 Nov 17;33(46):6351-9. doi: 10.1016/j.vaccine.2015.09.008. Epub 2015 Sep 15.
PubMed 26384447
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years
- ClinicalTrials.gov ID
- NCT01511250
- Acronym / sponsor ID
- INV-DEN-203
- Conditions
- Healthy
- Keywords
- Normal healthy adults and children, Safety and tolerability, Active vaccine, Placebo, Dengue virus vaccine, Immune response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2011 (actual)
- Primary completion
- 1 Apr 2016 (actual)
- Study completion
- 15 Apr 2016 (actual)
- First posted
- 18 Jan 2012 (estimated)
- Results
- Posted 27 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety of Takeda's tetravalent dengue vaccine (TDV) (previously DENVax) administered subcutaneously in healthy adults and children. In addition the antibody response to the four dengue virus serotypes will be evaluated.
Detailed description
The vaccine tested in this study was tetravalent dengue vaccine (TDV). TDV was tested to assess safety and immunogenicity in healthy adults and children living in dengue endemic countries.
The study enrolled 360 healthy participants. The study was conducted in 2 parts, Part 1 - age descending and and Part 2 - expansion - ages 1.5-11 years. Participants were allocated to one of the four age cohorts in Part 1 (21 to 45 years, 12 to 20 years, 6 to 11 years, and 1.5 to 5 years) and expansion age cohort 1.5-11 years in Part 2. Participants were randomized in 2:1 ratio and in 3: 1 ratio in Part 1 and 2 respectively to receive:
- TDV 0.5 mL SC injection
- Placebo (inactive solution) - this is a solution that looks like the study drug but has no active ingredient
This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 37 months (including screening period). Participants made multiple visits to the clinic including a final visit at Day 1080.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part I: TDV 21 to 45 Years (yrs) | Experimental | Biological: TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 plaque forming units (PFU), 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. |
| Part I: Placebo 21 to 45 yrs | Placebo comparator | Biological: PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| Part I: TDV 12 to 20 yrs | Experimental | Biological: TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. |
| Part I: Placebo 12 to 20 yrs | Placebo comparator | Biological: PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| Part I: TDV 6 to 11 yrs | Experimental | Biological: TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. |
| Part I: Placebo 6 to 11 yrs | Placebo comparator | Biological: PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| Part I: TDV 1.5 to 5 yrs | Experimental | Biological: TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. |
| Part I: Placebo 1.5 to 5 yrs | Placebo comparator | Biological: PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| Part II: TDV 1.5 to 11 yrs | Experimental | Biological: TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. |
| Part II: Placebo 1.5 to 11 yrs | Placebo comparator | Biological: PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
Who may qualify
- Ages
- 18 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- In good health as determined by medical history, physical examination including height and weight
- Normal safety laboratory values at screening
- Negative for human immunodeficiency virus-1 (HIV-1) antibodies, Hepatitis C antibodies \& Hepatitis B surface antigen
- Females negative by urine pregnancy test at screening and immediately prior to injection, and were willing to use reliable means of contraception
- Weight: Within 1.3 times of the upper limit of local normal age-adjusted body mass index (BMI)
Key exclusion criteria (9 listed)
- For participants ≥12 years, clinically significant electrocardiogram (ECG) findings
- History of significant dermatologic (skin) disease within last 6 months
- History of diabetes mellitus
- History of thymic pathology, thymectomy, myasthenia or any immunodeficiency
- History of recurring headaches or migraines
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDVTDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU. | Biological | Part I: TDV 1.5 to 5 yrs, Part I: TDV 12 to 20 yrs, Part I: TDV 21 to 45 Years (yrs), Part I: TDV 6 to 11 yrs, Part II: TDV 1.5 to 11 yrs |
| PlaceboTDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). | Biological | Part I: Placebo 1.5 to 5 yrs, Part I: Placebo 12 to 20 yrs, Part I: Placebo 21 to 45 yrs, Part I: Placebo 6 to 11 yrs, Part II: Placebo 1.5 to 11 yrs |
Primary outcome
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain [Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)] and itching (pruritus) [Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: >10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity
Time frame: Within 28 days after either of the vaccination given on Day 0 or 90 (Day 28 for first vaccination, Day 118 for second vaccination)
Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain [Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)] and itching (pruritus) [Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: >10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).
Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity
Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
Solicited systemic AEs (headache, muscle pain [myalgia], joint pain [arthralgia], eye pain, sensitivity to light [photophobia], tiredness [fatigue], body rash, nausea, were recorded in the participant's-diary along with vomiting [number of times]), and body temperature). Diary-recorded severity grades were based on the Common Terminology Criteria for Adverse Events (CTCAE). Severity grades were: Mild (Grade 1): transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities. The CTCAE severity grades for fever and vomiting were derived from the diary-recorded measurements of temperature level and number of episodes, respectively.
Number of Participants With Any Solicited AE Following Either Vaccination Dose
Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)
An 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. Solicited local injection site reactions included pain, itching, erythema, edema and solicited systemic AEs include myalgia, arthralgia, eye pain, photophobia, fatigue, body rash, nausea, vomiting, and fever.
Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity
Time frame: Unsolicited AEs were collected within 28 days of all vaccinations. Serious AEs were collected throughout the study up to Day 1080
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. The severity of all unsolicited AEs was evaluated by the Investigator (using the Common Terminology Criteria for Adverse Events [CTCAE] v4.03) as follows. Mild (Grade 1): Transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): Marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities.
Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120
Time frame: 30 days after second vaccination (Day 120)
Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralizing antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 for any serotype and seronegative was defined as titre value of less than (<) 10 for all 4 serotypes. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4.
8 secondary outcomes
Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination
Time frame: Days 0, 7, 14, 90, 97, and 104
Part I: Duration of Vaccine Viremia
Time frame: Days 0, 7, 14, 90, 97, and 104
Part I: Titers of Vaccine Viremia
Time frame: Days 0, 7, 14, 90, 97, and 104
Seropositivity Rate to Each of the Four Dengue Serotypes
Time frame: Day 28 and Day 90 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Seroconversion Rate to Each of the Four Dengue Serotypes
Time frame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
Time frame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1
Geometric Mean Fold Rise (GMFR) of Dengue Neutralizing Antibody Titers for Each of the 4 Dengue Serotypes
Time frame: Day 28 and Day 90 (Parts 1 and 2) and Days 120, 180, 360, 720 and 1080 in Part 1
Number of Participants With Confirmed Dengue Fever
Time frame: Day 1 to Day 1080
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42480195Gottardo R, Dean H, Nascimento EJM, Tricou V, Sharma M. Beyond neutralization: A comprehensive framework for evaluating humoral immunity induced by a live-attenuated tetravalent dengue vaccine. Vaccine. 2026 Aug 13;88:128929. doi: 10.1016/j.vaccine.2026.128929. Epub 2026 Jul 21.
- Derived from this study: PubMed 40099800Rauscher M, Youard Z, Faccin A, Patel SS, Pang H, Zent O. Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine. Expert Rev Vaccines. 2025 Dec;24(1):221-229. doi: 10.1080/14760584.2025.2480297. Epub 2025 Mar 27.
- Derived from this study: PubMed 36461942Nascimento EJM, Norwood B, Kpamegan E, Parker A, Fernandes J, Perez-Guzman E, Tricou V, Braun R, Sharma M, Dean HJ. Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System. J Infect Dis. 2023 May 29;227(11):1282-1292. doi: 10.1093/infdis/jiac476.
- Derived from this study: PubMed 33534885Tsuji I, Dominguez D, Egan MA, Dean HJ. Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine. J Infect Dis. 2022 May 4;225(9):1533-1544. doi: 10.1093/infdis/jiab064.
- Derived from this study: PubMed 32658250Sirivichayakul C, Barranco-Santana EA, Rivera IE, Kilbury J, Raanan M, Borkowski A, Papadimitriou A, Wallace D. Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study. J Infect Dis. 2022 May 4;225(9):1513-1520. doi: 10.1093/infdis/jiaa406.
- Derived from this study: PubMed 30783676Sharma M, Glasner DR, Watkins H, Puerta-Guardo H, Kassa Y, Egan MA, Dean H, Harris E. Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate. J Infect Dis. 2020 Mar 2;221(6):867-877. doi: 10.1093/infdis/jiz081.
- Derived from this study: PubMed 26384447Rupp R, Luckasen GJ, Kirstein JL, Osorio JE, Santangelo JD, Raanan M, Smith MK, Wallace D, Gordon GS, Stinchcomb DT. Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study. Vaccine. 2015 Nov 17;33(46):6351-9. doi: 10.1016/j.vaccine.2015.09.008. Epub 2015 Sep 15.
- To obtain more information about this study, click this link.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Takeda
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TDV in people with Healthy, run by Takeda at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Puerto Rico, Singapore, Thailand, Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity (time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01511250, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2023.