Dengue Fever
Conditions
Brief summary
Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.
Detailed description
Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN2/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 2 (DEN2). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN2/4delta30(ME) vaccine in healthy adults. This study will last approximately 5 to 7 months with 25 study visits. Participants will be randomly assigned into one of two cohorts. Participants in Cohort 1 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 180. Participants in Cohort 2 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 120. Participants will be asked to record their temperature in a diary for 16 days after each vaccination. At each study visit a physical examination, symptom history, and blood and urine collection will occur.
Interventions
BIOLOGICALrDEN2/4delta30(ME) vaccine
10\^3 PFU dose
BIOLOGICALPlacebo
placebo for rDEN2/4delta30(ME) vaccine
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Good general health as determined by means of the screening procedures. * Available for the duration of the study (32 weeks for cohort 1 and 23 weeks for cohort 2) * Willing to use effective methods of contraception
Exclusion criteria
* Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator will affect the ability of the volunteer to understand and cooperate with the requirements of the study protocol * Neutropenia as defined by an ANC ≤1500/mm3 * ALT level above the laboratory-defined upper limit of normal * Serum creatinine level above the laboratory-defined upper limit of normal * Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol. * Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months * History of a severe allergic reaction or anaphylaxis * Severe asthma (emergency room visit or hospitalization within the last 6 months) * Positive HIV-1 serology by screening and confirmatory assays * Positive for hepatitis C virus (HCV) by screening and confirmatory assays * Positive hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA) * Known immunodeficiency syndrome * Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study * Receipt of a live vaccine within the 4 weeks or a killed vaccine within the 2 weeks prior to entry into the study * Has had spleen surgically removed * Receipt of blood products within the 6 months prior to study entry * History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g. yellow fever virus, St. Louis encephalitis, West Nile virus). * Previous receipt of yellow fever or dengue vaccine (licensed or experimental) * Persons who have received any investigational agent in the 30 days prior to study entry * Persons who have definite plans to travel to a dengue endemic area during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the frequency of vaccine related AEs for each dose, graded by severity. | Throughout study |
| Compare the immunogenicity of the two 2-dose regimens of the rDEN2/4Δ30(ME) candidate vaccine as assessed by neutralizing antibody titers to DEN2 | At 4 and 6 weeks after each vaccination |
Secondary
| Measure | Time frame |
|---|---|
| Assess the frequency, quantity, and duration of viremia after each dose of vaccine. | Throughout study |
| Determine the number of vaccinees infected with rDEN2/4Δ30(ME) | Throughout study |
| Comparison of infectivity rates, safety, and immunogenicity between dose 1 and dose 2 withhin cohort and between cohorts | Throughout study |
| Evaluation of the phenotype and activation of peripheral blood mononuclear cells at primary infection and upon reinfection with the DEN2/4Δ30(ME) vaccine. | Throughout study |
Countries
United States
Outcome results
None listed