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

Takeda

Status and phase: Completed; Phase 2

Conditions: Healthy

Treatments: Biological: TDV; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01511250

INV-DEN-203

2022-003455-33 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 360 patients

Sex: All

Ages: 18 months to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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360 participants in 10 patient groups, including a placebo group

Part I: TDV 21 to 45 Years (yrs)

Experimental group

Description:

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.

Treatment:

Biological: TDV

Part I: Placebo 21 to 45 yrs

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo

Part I: TDV 12 to 20 yrs

Experimental group

Description:

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.

Treatment:

Biological: TDV

Part I: Placebo 12 to 20 yrs

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo

Part I: TDV 6 to 11 yrs

Experimental group

Description:

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.

Treatment:

Biological: TDV

Part I: Placebo 6 to 11 yrs

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo

Part I: TDV 1.5 to 5 yrs

Experimental group

Description:

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.

Treatment:

Biological: TDV

Part I: Placebo 1.5 to 5 yrs

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo

Part II: TDV 1.5 to 11 yrs

Experimental group

Description:

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.

Treatment:

Biological: TDV

Part II: Placebo 1.5 to 11 yrs

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo