Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue

NCT ID: NCT03423173

Last Updated: 2020-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 923 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-12
• Study Completion Date: 2019-01-14

Brief Summary

The purpose of this study is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive TDV lots in healthy participants aged 18 to 60 years in non-endemic country(ies) for dengue.

Detailed Description

The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). The primary objective of this trial is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive lots of TDV in healthy participants in non-endemic country(ies) for dengue.

The study will enroll approximately 924 healthy participants. Participants will be randomized in 2:2:2:1 to one of 4 trial groups to receive TDV (Lots 1, 2 or 3) or placebo:

• TDV 0.5 mL subcutaneous injection OR
• Placebo normal saline solution (0.9% NaCl) for injection.

In each trial group, all participants will receive 2 doses of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3). Immunogenicity will be assessed in participants included in the immunogenicity subset (TDV groups: 176 participants each and placebo group: 88 participants) and safety will be assessed in all participants in each group.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 270 days. Participants will make multiple visits to the clinic including a final visit at Day 270.

Conditions

Dengue Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

TDV Placebo-matching normal saline (0.9% NaCl) subcutaneous injection

TDV Lot 1

Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.

Group Type: EXPERIMENTAL

TAK-003

Intervention Type: BIOLOGICAL

TDV subcutaneous injection

TDV Lot 2

Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.

Group Type: EXPERIMENTAL

TAK-003

Intervention Type: BIOLOGICAL

TDV subcutaneous injection

TDV Lot 3

Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.

Group Type: EXPERIMENTAL

TAK-003

Intervention Type: BIOLOGICAL

TDV subcutaneous injection

Interventions

TAK-003

TDV subcutaneous injection

Intervention Type: BIOLOGICAL

Placebo

TDV Placebo-matching normal saline (0.9% NaCl) subcutaneous injection

Intervention Type: BIOLOGICAL

Other Intervention Names

TDV

Eligibility Criteria

Inclusion Criteria

1. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.

2. 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.

Exclusion Criteria

1. Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.

2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccine or placebo).

3. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).

4. Known or suspected impairment/alteration of immune function, including:

1. 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 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed)

2. 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 (M0).

3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.

4. Receipt of immunostimulants within 60 days prior to Day 1 (M0).

5. Hepatitis C virus infection.

6. Genetic immunodeficiency.

5. Has abnormalities of splenic or thymic function.

6. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

7. Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).

8. Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg/[height in meters^2]).

9. Has history of substance or alcohol abuse within the past 2 years.

10. Had previous and planned vaccination (during the trial conduct) against any flavivirus including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.

11. Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile (WN) fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Optimal Research

Huntsville, Alabama, United States

Anaheim Clinical Trials, LLC

Anaheim, California, United States

Advanced Clinical Research

Boise, Idaho, United States

Optimal Research

Peoria, Illinois, United States

Synexus Limited- Council Bluffs

Council Bluffs, Iowa, United States

Heartland Research Associates LLC - Augusta

Augusta, Kansas, United States

Heartland Research Associates LLC

Park City, Kansas, United States

Optimal Research

Rockville, Maryland, United States

Synexus Limited - Minneapolis

Edina, Minnesota, United States

Synexus Limited - St. Louis

St Louis, Missouri, United States

Clinical Research Center of Nevada

Las Vegas, Nevada, United States

Synexus Limited - Columbus

Columbus, Ohio, United States

Advanced Clinical Research

Salt Lake City, Utah, United States

Advanced Clinical Research

West Jordan, Utah, United States

Countries

United States

References

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)

Tricou V, Winkle PJ, Tharenos LM, Rauscher M, Escudero I, Hoffman E, LeFevre I, Borkowski A, Wallace D. Consistency of immunogenicity in three consecutive lots of a tetravalent dengue vaccine candidate (TAK-003): A randomized placebo-controlled trial in US adults. Vaccine. 2023 Nov 13;41(47):6999-7006. doi: 10.1016/j.vaccine.2023.09.049. Epub 2023 Oct 24.

Reference Type: DERIVED

PMID: 37884415 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DEN-304

Identifier Type: -

Identifier Source: org_study_id