A Phase I Evaluation of the Safety and Immunogenicity of rDEN2/4 Δ30(ME) Dengue Serotype 2 Vaccine Given at 10^1 PFU in Healthy Flavivirus-naïve Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Dengue Virus
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Immunogenicity of vaccine, as assessed by neutralizing antibody titers
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will test whether a vaccine developed to prevent infection with dengue virus type 2 causes a response in people's immune system and is safe.
Detailed Description
Dengue viruses cause approximately 50 million cases of dengue fever and 1.5 million cases of the more severe diseases dengue hemorrhagic fever (DHS) and dengue shock syndrome (DSS) every year. There are four subtypes of the virus, and infection with one offers no protection from infection by the others. In fact, most cases of DHS and DSS occur in people infected by more than one subtype. In areas of the world where multiple subtypes of dengue are common, vaccines must be developed against each of the subtypes of dengue virus. This study will examine the safety and immune response of an investigational vaccine for preventing dengue virus type 2. Participation in this study will last about 6 weeks. Participants will be randomly assigned to be injected with either the investigational study vaccine or a placebo. Participants will have a five in six chance of receiving the vaccine. The first study visit will take place on the vaccination day, on which participants will undergo a physical examination, blood draw, and pregnancy test and then receive the vaccine. Participants will be given a thermometer and temperature card and be told to record their temperatures three times per day for 16 days after vaccination. Participants will come to follow-up visits every other day for the 16 days after vaccination and then 3, 4, and 6 weeks after vaccination (Days 21, 28, and 42). Assessments completed during these visits will include a questionnaire about how the participant is feeling, pregnancy test, review of temperature cards, blood draw, and physical exam. Blood drawn will be analyzed to check participants' health, determine the amount of vaccine and antibodies in the blood, test markers in white blood cells and genes, and look for proteins that are important for fighting dengue infection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Good general health as determined by physical examination, laboratory screening, and review of medical history
- •Available for the duration of the study, approximately 6 weeks post-vaccination
- •Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial
Exclusion Criteria
- •Currently breastfeeding or pregnant
- •Exhibits evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
- •Presence of a behavioral, cognitive, or psychiatric disease that affects the ability of the participant to understand and cooperate with the requirements of the study protocol
- •Has screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in protocol
- •Presence of any condition that would jeopardize the safety or rights of the participant or would render the participant unable to comply with the protocol
- •Significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by participant history
- •History of a severe allergic reaction or anaphylaxis
- •Presence of severe asthma, defined as requiring emergency room visit or hospitalization within the last 6 months
- •Presence of HIV infection, determined by screening and confirmatory assays
- •Presence of hepatitis C virus (HCV) infection, determined by screening and confirmatory assays
Outcomes
Primary Outcomes
Immunogenicity of vaccine, as assessed by neutralizing antibody titers
Time Frame: Measured at 4 and 6 weeks after vaccination
Safety of vaccine, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity
Time Frame: Measured throughout study
Number of vaccinees infected with this dengue virus subtype 2 (DEN2) candidate vaccine, as defined by either recovery of vaccine virus from the blood of vaccinated participants and/or by seroconversion to DEN2
Time Frame: Measured at Days 28 and 42
Secondary Outcomes
- Frequency, quantity, and duration of viremia(Measured after vaccination)
- Comparison of infectivity rates, safety, and immunogenicity of a single dose of DEN2 vaccine from this trial to those variables on previous trials(Measured at study completion)