Clinical trial NCT01542632: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: safety and immunogenicity of dengue vaccine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-03-02
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


Eligibility 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

Primary outcomes:
measure: Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported
timeFrame: Day 0 to Day 104
measure: Number of Participants With at Least 1 Adverse Event Following Either Vaccine Dose
timeFrame: For 30 days after each dose (Up to Day 120)
measure: Number of Participants With at Least 1 Adverse Events Related to TDV Following Either Vaccine Dose
timeFrame: For 30 days after each dose (Up to Day 120)
measure: Rate of Seroconversion to Each of Four Dengue Serotypes
timeFrame: Up to 30 days after the last immunization (Up to Day 120)
Secondary outcomes:
measure: Percentage of Participants With Serotype-Specific TDV Viral RNA Detected After First and Second Vaccinations
timeFrame: various timepoints up to 30 days after each dose (Up to Day 120)
measure: Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes
timeFrame: Days 30, 90 and 120 after 1st vaccination
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Heart Center of the Rockies
state: Colorado
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
Study officials:
affiliation: Inviragen Inc.
name: Gilad Gordon, MD
role: STUDY_DIRECTOR
References: