Safety and Immunogenicity of Three Formulations of Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

NCT02193087 | Completed Phase 2 Results

• 2 other identifiers: DEN-106U1111-1154-9746
• Study Type: interventional
• Target: 1,002
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the equivalence of the lyophilized formulation of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) compared with the liquid formulation of TDV.

Conditions

Dengue Fever

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Geometric Mean Titer (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes Comparing Group D To Groups A and B Combined

  Geometric mean titer (GMT) of neutralizing antibodies for each of the four dengue serotypes as measured by Plaque Reduction Neutralization Test resulting in 50% reduction in Plaques (PRNT50). The four dengue serotypes are DEN-1, DEN-2, DEN-3 and DEN-4. A 90% Confidence Interval (CI) for the ratio of GMT (or equivalently the difference of the log transformed GMT) was provided, for each serotype, for the comparison of the lyophilized formulation (Group D) versus the liquid formulation 1 (Groups A+B combined). An Analysis of Variance (ANOVA) model for the natural log-transformed GMT at month 1 with study group as a factor was used for analysis.

  Month 1

Secondary Outcomes (10)

• Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes Comparing Group D With Group B

  Months 1 and 4

• Percentage of Participants With a Seropositive Response for Each of the Four Dengue Serotypes Comparing Group D With Groups A and B Combined

  Month 1

• Percentage of Participants With a Seropositive Response for Each of the Four Dengue Serotypes Comparing Group D With Group B

  Months 1 and 4

• Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs)

  Days 1 through 7 after each vaccination

• Percentage of Participants With Solicited Systemic Adverse Events (AEs)

  Days 1 through 14 after each vaccination

Study Arms (4)

Group A: TDV Liquid + Placebo

ACTIVE COMPARATOR

Takeda's Tetravalent Dengue Vaccine Candidate (TDV) Liquid Formulation 1, diluted 1:5 with vaccine diluent, subcutaneous injection on Day 1, and TDV Liquid Formulation placebo-matching solution, subcutaneous injection, once on Day 90 (Month 3).

Drug: TDV Liquid Formulation 1; Drug: Placebo

Group B: TDV Liquid

ACTIVE COMPARATOR

TDV Liquid Formulation 1, diluted 1:5 with vaccine diluent, subcutaneous injection on Day 1 and Day 90 (Month 3).

Drug: TDV Liquid Formulation 1

Group C: TDV Liquid

EXPERIMENTAL

TDV Liquid Formulation 2, subcutaneous injection on Day 1 and Day 90 (Month 3).

Drug: TDV Liquid Formulation 2

Group D: TDV Lyophilized

EXPERIMENTAL

TDV Lyophilized Formulation reconstituted with water, subcutaneous injection on Day 1 and Day 90 (Month 3).

Drug: TDV IDT Lyophilized

Interventions

TDV Liquid Formulation 1 DRUG

TDV Liquid Formulation 1 for subcutaneous injection

Group A: TDV Liquid + Placebo; Group B: TDV Liquid

TDV Liquid Formulation 2 DRUG

TDV Liquid Formulation 2 for subcutaneous injection

Group C: TDV Liquid

TDV IDT Lyophilized DRUG

TDV Lyophilized Formulation for subcutaneous injection

Group D: TDV Lyophilized

Placebo DRUG

TDV liquid formulation placebo-matching solution for subcutaneous injection

Group A: TDV Liquid + Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is aged 18 to 49 years, at the time of enrollment inclusive.
• Individuals who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
• Signs and dates a written, informed consent form 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.
• Individuals who can comply with trial procedures and are available for the duration of follow-up.

You may not qualify if:

• Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrollment. Trial entry should be delayed until the illness has improved.
• History or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components; b. Individuals with history of substance or alcohol abuse within the past 6 months; c. Female participants who are pregnant or breastfeeding; d. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome); e. Known or suspected impairment/alteration of immune function, including: i. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed); Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1; iii. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial; iv. Receipt of immunostimulants within 60 days prior to Day 1; v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months preceding (first) vaccination; vi. human immunodeficiency virus (HIV) infection or HIV-related disease; vii. Genetic immunodeficiency.
• Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration.
• Individuals participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
• Individuals who are first degree relatives of individuals involved in trial conduct.
• If female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to trial entry: a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal (for at least 2 years), bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy; b. Acceptable birth control methods are defined as one or more of the following: i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; iii. Intrauterine device (IUD); iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
• If female of childbearing potential, sexually active and refuses to use an acceptable contraceptive method through to 6 weeks after the last dose of investigational vaccine.
• Individuals with body mass index (BMI) greater than or equal to 35.
• Participants who received previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF), West Nile (WN), Japanese Encephalitis (JE), and St. Louis encephalitis.
• Documented or suspected disease caused by dengue, JE, WN, YF virus, and/or St. Louis encephalitis.
• History of travel to dengue endemic areas including the Caribbean, Mexico, Central America, South America or Southeast Asia during the 6 months prior to screening or planned travel to a dengue endemic area during the study period.
• Clinically significant abnormality in the screening laboratory tests as judged by the Investigator.
• History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines.
• Blood tests positive for antibodies to HIV-1/2, Hepatitis C and Hepatitis B surface antigen.

Sponsors & Collaborators

• Takeda: lead

Study Sites (7)

Hope Research Institute

Phoenix, Arizona, 85018, United States

Location

Anaheim Clinical Trials, LLC

Anaheim, California, 92805, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

Advanced Clinical Research

Meridian, Idaho, 83462, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Clinical Research Center of Nevada

Las Vegas, Nevada, 89104, United States

Location

Tekton Research

Austin, Texas, 78745, United States

Location

Related Publications (2)

• 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

• Turner M, Papadimitriou A, Winkle P, Segall N, Levin M, Doust M, Johnson C, Lucksinger G, Fierro C, Pickrell P, Raanan M, Tricou V, Borkowski A, Wallace D. Immunogenicity and safety of lyophilized and liquid dengue tetravalent vaccine candidate formulations in healthy adults: a randomized, phase 2 clinical trial. Hum Vaccin Immunother. 2020 Oct 2;16(10):2456-2464. doi: 10.1080/21645515.2020.1727697. Epub 2020 Mar 2.

  PMID: 32119591 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Medical Director Clinical Science, Study Official
• 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: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: July 17, 2014
• Study Start: August 6, 2014
• Primary Completion: May 19, 2015
• Study Completion: May 19, 2015
• Last Updated: July 18, 2019
• Results First Posted: June 29, 2016

Record last verified: 2019-07

Locations

US (7)