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

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Phase 1b Study to Investigate the Safety and Immunogenicity of Various Schedules of Tetravalent Chimeric Dengue Vaccine in Healthy Adult Volunteers Between the Ages of 18 - 45 Years

Conditions
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Healthy

Intervention / Treatment
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* Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
* Biological: TDV New Formulation
* Drug: Placebo
* Drug: New Formulation Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at least 18 years and ≤ 45 years old at time of screening In good health as determined by medical history, physical examination including height and weight 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)]. Weight: Body Mass Index (BMI) ≤32 Blood tests negative for antibodies to Human Immuno-virus (HIV-1), Hepatitis C, and Hepatitis B surface antigen Exclusion Criteria: Any condition which would limit the subject's ability to complete the study in the opinion of the Investigator Clinically significant ECG findings History of any significant dermatologic disease in the last 6 months, History of diabetes mellitus History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines Hypersensitivity to any vaccine Receipt of any vaccine in the 4 weeks preceding the first vaccination Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study Known history of Japanese Encephalitis Virus (JEV) and/or Yellow Fever (YF) Previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF) and Japanese Encephalitis (JE) Seropositivity to dengue or West Nile (WN) virus Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months 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 Use of any non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen or antihistamines for the 3 days immediately prior to each vaccination 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) Positive urine screen for cocaine, amphetamines, opiates, or cannabinoids Donation of blood 6 weeks before the first dose(s) (Day 0) until 30 days after the dose on day 90 Females who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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. | Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)<br>* TDV subcutaneous injection<br>Drug: Placebo<br>* Placebo subcutaneous injection<br>|
| Experimental: Group 2<br>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. | Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)<br>* TDV subcutaneous injection<br>Drug: Placebo<br>* Placebo subcutaneous injection<br>|
| Experimental: Group 3<br>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. | Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)<br>* TDV subcutaneous injection<br>|
| Experimental: Group 4<br>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. | Biological: TDV New Formulation<br>* TDV New Formulation subcutaneous injection<br>Drug: New Formulation Placebo<br>* New Formulation placebo subcutaneous injection<br>|
| Experimental: Group 5<br>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. | Biological: TDV New Formulation<br>* TDV New Formulation subcutaneous injection<br>Drug: New Formulation Placebo<br>* New Formulation placebo subcutaneous injection<br>|
| Experimental: Group 6<br>1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90. | Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)<br>* TDV subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported | Erythema and Edema Were Graded Per The FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Where Grade 0=none to Grade 4=Severe. Pain and Itching were graded using Common Terminology Criteria for Adverse Events (CTCAE) 4.03 where Grade 0=no pain or itching to Grade 4= Life-threatening/severe. Only those score categories for which there was at least 1 participant are reported. | Day 0 to Day 104 | 
| Number of Participants With at Least 1 Adverse Event Following Either Vaccine Dose | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | For 30 days after each dose (Up to Day 120) | 
| Number of Participants With at Least 1 Adverse Events Related to TDV Following Either Vaccine Dose | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. Some AEs are automatically considered related because of temporal relationship to vaccination. | For 30 days after each dose (Up to Day 120) | 
| Rate of Seroconversion to Each of Four Dengue Serotypes | Rate of seroconversion was defined as the percentage of participants with Plaque Reduction Neutralization Test titer resulting in 50 % reduction in Plagues (PRNT50) titer ≥ 10 for participants seronegative at Baseline or a greater than four-fold increase in PRNT50 for participants seropositive at Baseline. | Up to 30 days after the last immunization (Up to Day 120) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Serotype-Specific TDV Viral RNA Detected After First and Second Vaccinations | Serotype-Specific TDV Viral RNA was assessed for the four dengue serotypes: Dengue-1, Dengue-2, Dengue-3 and Dengue-4 . Only those serotypes and time-points where at least 1 participant had Serotype-Specific TDV Viral RNA Detected is reported. | various timepoints up to 30 days after each dose (Up to Day 120) | 
| Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes |  | Days 30, 90 and 120 after 1st vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety and immunogenicity of dengue vaccine