A Phase 1 Evaluation of the Safety and Immunogenicity of Five Admixtures of TetraVax-DV, a Recombinant Live Attenuated Tetravalent Dengue Virus Vaccine, in Healthy Flavivirus-naïve Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Dengue
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 141
- Locations
- 3
- Primary Endpoint
- Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity
- 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 evaluate the safety and immune responses of five formulations of a tetravalent dengue virus vaccine in healthy adults.
Detailed Description
Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of five versions of a live, attenuated, tetravalent dengue virus vaccine called TetraVax-DV. This study will enroll healthy adults 18-50 years old. Participants will be randomly assigned to receive one of the five versions of TetraVax-DV or placebo. At the vaccination study visit, participants will undergo a medical history review, physical examination, blood and urine collection, and vital sign measurements. Participants will then receive one injection of their assigned vaccine or placebo in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation. At home, participants will monitor and record their temperature three times a day for 16 days. Additional study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 42, and 180 for physical exams, assessment of symptoms, and blood and urine collection. Some participants will attend an additional study visit at Day 60. Participants who received one of the five versions of the vaccine will be asked to take part in an optional substudy that will evaluate the safety and immunogenicity of a second vaccination 6 months after the first vaccination. In the substudy, participants will be randomly assigned to receive either the same vaccine they received in the first part of the study or a placebo vaccine. For 6 months following the second vaccination, participants will attend study visits and take part in the same study procedures that occurred in the first part of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In good general health, as determined by physical examination, laboratory screening, and review of medical history
- •Available for the duration of the study, approximately 26 weeks post-vaccination
- •Willing to participate in the study as evidenced by signing the informed consent document
- •Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.
Exclusion Criteria
- •Pregnant or breastfeeding
- •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 affects the person's ability to understand and cooperate with the requirements of the study
- •Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol
- •Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
- •Any significant alcohol or drug abuse in the 12 months before study entry which has caused medical, occupational, or family problems, as indicated by medical history
- •History of a severe allergic reaction or anaphylaxis
- •Severe asthma (emergency room visit or hospitalization in the 6 months before study entry)
- •HIV infection, by screening and confirmatory assays
- •Hepatitis C virus (HCV) infection, by screening and confirmatory assays
Outcomes
Primary Outcomes
Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity
Time Frame: Measured out to Day 28
Determination of the serum plaque reduction neutralization titer 60% (PRNT_60) to DEN1, DEN2, DEN3, and DEN4 viruses
Time Frame: Measured at Days 0, 28, 42, and 180
Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates
Time Frame: Measured at 4 and 6 weeks after vaccination
Seropositivity and seroconversion rates to greater than 60% in in the TetraVax-DV admixture 5 vaccine arm
Time Frame: Measured by Day 42
Secondary Outcomes
- Duration of the neutralizing antibody response(Measured at Day 180)
- Frequency, quantity, and duration of viremia following vaccination(Measured out to Day 21)
- Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4(Measured by Day 42)
- Safety and immunogenicity of a second dose of vaccine given 6 months after the first dose (optional substudy)(Measured at Day 222 (42 days after second dose))
- Seroconversion as assessed by a greater than or equal to 4-fold rise in DEN1, DEN2, DEN3, or DEN4 neutralizing antibody titers compared with the pre-vaccination antibody titer(Measured by Day 42)
- Seropositivity as assessed by PRNT_60 to DEN1, DEN2, DEN3, DEN4 greater than or equal to 1:10 compared with the pre-vaccination titer(Measured by Day 42)