A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers

Takeda

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV); Drug: Placebo; Drug: New Formulation Placebo; Biological: TDV New Formulation

Study type: Interventional

Funder types: Industry

Identifiers

NCT01542632

U1111-1177-8166 (Registry Identifier)

INV-DEN-104

Details and patient eligibility

About

A Phase 1 study to compare the safety, tolerability and immunogenicity of different dose schedules of subcutaneously (SC) administered dengue vaccine in healthy adults and to compare the immunogenicity of different dose schedules of the vaccine.

Blood samples were obtained for safety labs on Days 0, 7, 14, 90, 97, 104 and measurement of viremia at baseline [during the screening period or on day of vaccination (Day 0)], and then on Days 7, 9, 11, 14, 17, 21, 90, 97, and 104. Blood samples for measurement of dengue neutralizing antibodies in serum were obtained at baseline [during the screening period or on day of vaccination (Day 0)], then on Days 30, 90 and 120.

The entire duration for each individual subjects participation was approximately 5 months including recruitment and collection of data for primary outcomes (through Day 120).

Enrollment: 140 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male or female at least 18 years and ≤ 45 years old at time of screening
2. In good health as determined by medical history, physical examination including height and weight
3. Normal clinical safety laboratory examinations [Sodium (Na), Potassium (K), Glucose, Blood Urea Nitrogen (BUN), creatinine, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin, White Blood Cell (WBC), neutrophil count, hemoglobin, platelets, Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and urinalysis (by dipstick)].
4. Weight: Body Mass Index (BMI) ≤32
5. Blood tests negative for antibodies to Human Immuno-virus (HIV-1), Hepatitis C, and Hepatitis B surface antigen

Exclusion criteria

1. Any condition which would limit the subject's ability to complete the study in the opinion of the Investigator
2. Clinically significant ECG findings
3. History of any significant dermatologic disease in the last 6 months,
4. History of diabetes mellitus
5. History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines
6. Hypersensitivity to any vaccine
7. Receipt of any vaccine in the 4 weeks preceding the first vaccination
8. Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study
9. Known history of Japanese Encephalitis Virus (JEV) and/or Yellow Fever (YF)
10. Previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF) and Japanese Encephalitis (JE)
11. Seropositivity to dengue or West Nile (WN) virus
12. Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months
13. Use within the previous 6 months of systemic corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Topical prednisone is not permitted if currently in use or within the last 3 months. Note, inhaled prednisone (or equivalent) is allowed
14. Use of any non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen or antihistamines for the 3 days immediately prior to each vaccination
15. Use of any prescription or over the counter medications (besides those specifically mentioned above or those required for medical management of concurrent diseases) 7 days before the first vaccination (Day 0)
16. Positive urine screen for cocaine, amphetamines, opiates, or cannabinoids
17. Donation of blood 6 weeks before the first dose(s) (Day 0) until 30 days after the dose on day 90
18. Females who are pregnant or lactating

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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140 participants in 6 patient groups

Group 1

Experimental group

Description:

Takeda's Tetravalent Dengue Vaccine Candidate (TDV), 0.5 mL, subcutaneous injection in one arm and placebo, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.

Treatment:

Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Drug: Placebo

Group 2

Experimental group

Description:

TDV, 0.5 mL, subcutaneous injection in one arm and TDV 0.5 mL, subcutaneous injection in the other arm on Day 0. Placebo, 0.5 mL, subcutaneous injection on Day 90.

Treatment:

Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Drug: Placebo

Group 3

Experimental group

Description:

TDV, 0.5 mL, subcutaneous injection in one arm and TDV, 0.5 mL, subcutaneous injection in the other arm on Day 0. TDV, 0.5 mL, subcutaneous injection on Day 90.

Treatment:

Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Group 4

Experimental group

Description:

TDV new formulation, 0.5 mL, subcutaneous injection in one arm and new formulation placebo, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.

Treatment:

Drug: New Formulation Placebo

Biological: TDV New Formulation

Group 5

Experimental group

Description:

TDV new formulation, 0.5 mL, subcutaneous injection in one arm and TDV new formulation, 0.5 mL, subcutaneous injection in the other arm on Days 0 and 90.

Treatment:

Drug: New Formulation Placebo

Biological: TDV New Formulation

Group 6

Experimental group

Description:

1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.

Treatment:

Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)