Back to resultsA Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers
Primary Purpose
Healthy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
TDV New Formulation
Placebo
New Formulation Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Healthy focused on measuring safety and immunogenicity of dengue vaccine
Eligibility Criteria
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
Sites / Locations
- Heart Center of the Rockies
- University of Texas Medical Branch
- Advanced Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
Arm 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.
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.
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.
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.
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.
1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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.
Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01542632
Brief Title
A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
February 1, 2012 (Actual)
Primary Completion Date
January 1, 2014 (Actual)
Study Completion Date
January 10, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
Keywords
safety and immunogenicity of dengue vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm 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.
Arm Title
Group 2
Arm Type
Experimental
Arm 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.
Arm Title
Group 3
Arm Type
Experimental
Arm 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.
Arm Title
Group 4
Arm Type
Experimental
Arm 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.
Arm Title
Group 5
Arm Type
Experimental
Arm 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.
Arm Title
Group 6
Arm Type
Experimental
Arm Description
1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.
Intervention Type
Biological
Intervention Name(s)
Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
Intervention Description
TDV subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
TDV New Formulation
Intervention Description
TDV New Formulation subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
New Formulation Placebo
Intervention Description
New Formulation placebo subcutaneous injection
Primary Outcome Measure Information:
Title
Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported
Description
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.
Time Frame
Day 0 to Day 104
Title
Number of Participants With at Least 1 Adverse Event Following Either Vaccine Dose
Description
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.
Time Frame
For 30 days after each dose (Up to Day 120)
Title
Number of Participants With at Least 1 Adverse Events Related to TDV Following Either Vaccine Dose
Description
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.
Time Frame
For 30 days after each dose (Up to Day 120)
Title
Rate of Seroconversion to Each of Four Dengue Serotypes
Description
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.
Time Frame
Up to 30 days after the last immunization (Up to Day 120)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Serotype-Specific TDV Viral RNA Detected After First and Second Vaccinations
Description
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.
Time Frame
various timepoints up to 30 days after each dose (Up to Day 120)
Title
Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
Time Frame
Days 30, 90 and 120 after 1st vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilad Gordon, MD
Organizational Affiliation
Inviragen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Heart Center of the Rockies
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
Advanced Clinical Research
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers
We'll reach out to this number within 24 hrs