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

NCT01511250 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: INV-DEN-2032022-003455-33
• Study Type: interventional
• Target: 360
• Locations: 4 countries
• Sites: 8

Brief 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.

Conditions

Healthy

Keywords

Normal healthy adults and children; Safety and tolerability; Active vaccine; Placebo; Dengue virus vaccine; Immune response

Outcome Measures

Primary Outcomes (6)

• 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).

  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).

  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.

  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.

  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.

  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.

  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

  Days 0, 7, 14, 90, 97, and 104

• Part I: Duration of Vaccine Viremia

  Days 0, 7, 14, 90, 97, and 104

• Part I: Titers of Vaccine Viremia

  Days 0, 7, 14, 90, 97, and 104

• Seropositivity Rate to Each of the Four Dengue Serotypes

  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

  Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

Study Arms (10)

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.

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).

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.

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).

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.

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).

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.

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).

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.

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).

Biological: Placebo

Interventions

TDV 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: 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

Placebo BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Takeda: lead

Study Sites (8)

Program For The Study and Control of Tropical Diseases

Medellín, Colombia

Location

Ponce School of Medicine, CAIMED Center

Ponce, 716, Puerto Rico

Location

University of Puerto Rico School of Medicine

San Juan, 00935, Puerto Rico

Location

Latin Clinical Trial Center

San Juan, 909, Puerto Rico

Location

National University Hospital

Singapore, 119228, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Faculty of Tropical Medicine, Mahidol University

Bangkok, Bangkok, 10270, Thailand

Location

Phramongkutklao Hospital

Bangkok, Bangkok, 10400, Thailand

Location

Related Publications (6)

• 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.

  PMID: 40099800 DERIVED

• 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.

  PMID: 36461942 DERIVED

• 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.

  PMID: 33534885 DERIVED

• 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.

  PMID: 32658250 DERIVED

• 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.

  PMID: 30783676 DERIVED

• 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.

  PMID: 26384447 DERIVED

Related Links

• To obtain more information about this study, click this link.

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: January 18, 2012
• Study Start: November 16, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 15, 2016
• Last Updated: April 12, 2023
• Results First Posted: March 27, 2018

Record last verified: 2023-04

Locations

TH (2); CO (1); SG (2); PR (3)