Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years

NCT ID: NCT01511250

Last Updated: 2023-04-12

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-16

Study Completion Date

2016-04-15

Brief Summary

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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

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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

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Part I: TDV 21 to 45 Years (yrs)

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.

Group Type EXPERIMENTAL

TDV

Intervention Type BIOLOGICAL

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.

Part I: Placebo 21 to 45 yrs

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

TDV 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

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.

Group Type EXPERIMENTAL

TDV

Intervention Type BIOLOGICAL

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.

Part I: Placebo 12 to 20 yrs

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

TDV 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

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.

Group Type EXPERIMENTAL

TDV

Intervention Type BIOLOGICAL

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.

Part I: Placebo 6 to 11 yrs

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

TDV 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

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.

Group Type EXPERIMENTAL

TDV

Intervention Type BIOLOGICAL

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.

Part I: Placebo 1.5 to 5 yrs

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

TDV 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

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.

Group Type EXPERIMENTAL

TDV

Intervention Type BIOLOGICAL

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.

Part II: Placebo 1.5 to 11 yrs

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Interventions

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TDV

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.

Intervention Type BIOLOGICAL

Placebo

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
* For participants ≥12 years, positive urine screen for cocaine, amphetamines, opiates, or cannabinoids
* History of alcohol abuse
* Pregnant or lactating female
Minimum Eligible Age

18 Months

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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Program For The Study and Control of Tropical Diseases

Medellín, , Colombia

Site Status

Ponce School of Medicine, CAIMED Center

Ponce, , Puerto Rico

Site Status

University of Puerto Rico School of Medicine

San Juan, , Puerto Rico

Site Status

Latin Clinical Trial Center

San Juan, , Puerto Rico

Site Status

National University Hospital

Singapore, , Singapore

Site Status

Changi General Hospital

Singapore, , Singapore

Site Status

Faculty of Tropical Medicine, Mahidol University

Bangkok, Bangkok, Thailand

Site Status

Phramongkutklao Hospital

Bangkok, Bangkok, Thailand

Site Status

Countries

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Colombia Puerto Rico Singapore Thailand

References

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Rauscher 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.

Reference Type DERIVED
PMID: 40099800 (View on PubMed)

Nascimento 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.

Reference Type DERIVED
PMID: 36461942 (View on PubMed)

Tsuji 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.

Reference Type DERIVED
PMID: 33534885 (View on PubMed)

Sirivichayakul 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.

Reference Type DERIVED
PMID: 32658250 (View on PubMed)

Sharma 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.

Reference Type DERIVED
PMID: 30783676 (View on PubMed)

Rupp 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.

Reference Type DERIVED
PMID: 26384447 (View on PubMed)

Related Links

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Other Identifiers

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2022-003455-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INV-DEN-203

Identifier Type: -

Identifier Source: org_study_id

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