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

Takeda

Status and phase: Completed; Phase 3

Conditions: Dengue Fever

Treatments: Biological: TAK-003; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03423173

DEN-304

Details and patient eligibility

About

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.

Full 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.

Enrollment: 923 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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923 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo

TDV Lot 1

Experimental group

Description:

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.

Treatment:

Biological: TAK-003

TDV Lot 2

Experimental group

Description:

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.

Treatment:

Biological: TAK-003

TDV Lot 3

Experimental group

Description:

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.

Treatment:

Biological: TAK-003