Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01542632
First received: February 27, 2012
Last updated: December 31, 2014
Last verified: December 2014
  Purpose

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).


Condition Intervention Phase
Healthy
Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
Biological: TDV New Formulation
Drug: Placebo
Drug: New Formulation Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported [ Time Frame: Day 0 to Day 104 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: For 30 days after each dose (Up to Day 120) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: For 30 days after each dose (Up to Day 120) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 30 days after the last immunization (Up to Day 120) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: various timepoints up to 30 days after each dose (Up to Day 120) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 30, 90 and 120 after 1st vaccination ] [ Designated as safety issue: Yes ]

Enrollment: 140
Study Start Date: January 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
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)
TDV subcutaneous injection
Drug: Placebo
Placebo subcutaneous injection
Experimental: Group 2
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)
TDV subcutaneous injection
Drug: Placebo
Placebo subcutaneous injection
Experimental: Group 3
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)
TDV subcutaneous injection
Experimental: Group 4
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
TDV New Formulation subcutaneous injection
Drug: New Formulation Placebo
New Formulation placebo subcutaneous injection
Experimental: Group 5
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
TDV New Formulation subcutaneous injection
Drug: New Formulation Placebo
New Formulation placebo subcutaneous injection
Experimental: Group 6
1/10 TDV, 0.5 mL, subcutaneous injection on Days 1 and 90.
Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
TDV subcutaneous injection

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01542632

Locations
United States, Colorado
Poudre Valley Health System
Fort Collins, Colorado, United States
United States, Texas
Univ of Texas Medical Branch
Galveston, Texas, United States
United States, Utah
Advanced Clinical Research
Salt Lake City, Utah, United States, 84088
Sponsors and Collaborators
Takeda
Investigators
Study Director: Gilad Gordon, MD Inviragen Inc.
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01542632     History of Changes
Other Study ID Numbers: INV-DEN-104
Study First Received: February 27, 2012
Results First Received: December 31, 2014
Last Updated: December 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
safety and immunogenicity of dengue vaccine

ClinicalTrials.gov processed this record on February 27, 2015