Dengue
Conditions
Brief summary
Dengue viruses can cause dengue fever and other more severe forms of disease. This study will evaluate the safety and immune response to two doses of a dengue virus vaccine given 12 months apart in healthy adults.
Detailed description
Dengue viruses are a major health concern, particularly in the tropical and subtropical regions of the world. The World Health Organization (WHO) has made the development of a dengue vaccine a top priority. There are four types of dengue viruses (DEN1, DEN2, DEN3, and DEN4), each of which can cause various illnesses, including dengue fever, or the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). This study will evaluate the safety and immune response to two doses of a dengue virus vaccine (TV003) when administered 12 months apart in healthy adults. The study will also evaluate whether the candidate vaccine may protect against all four types of dengue viruses. Participants will be randomly assigned to receive the TV003 study vaccine or placebo vaccine. At study entry, participants will undergo a blood collection and physical examination, and female participants will take a pregnancy test. Participants will then receive an injection of their assigned vaccine. They will take their temperature three times a day for 16 days after each vaccination and record the results on a diary card, which research staff will review during participants' study visits. Additional study visits will occur on Days 3, 10, 14, 21, 28, 56, 90, 180, 270, and 330. All study visits will include blood collection and a physical examination; select visits will include a pregnancy test for female participants. At a study visit on Day 360, all participants will receive an injection of the same vaccine they received at study entry. Additional study visits will occur on Days 363, 370, 374, 381, 388, 416, 450, and 540, and will include the same study procedures as previously performed.
Interventions
BIOLOGICALTV003 Vaccine
TV003 will contain an admixture of the following monovalent dengue vaccines: 10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30(ME), 10\^3 PFU of rDEN3Δ30/31-7164, and 10\^3 PFU of rDEN4Δ30. TV003 vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.
BIOLOGICALPlacebo Vaccine
Placebo vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 26 weeks post-second vaccination * Willingness to participate in the study as evidenced by signing the informed consent document * Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.
Exclusion criteria
* Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, 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 ability of the participant to understand and cooperate with the requirements of the study protocol * Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol * Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol * Any 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 * Severe asthma (emergency room visit or hospitalization within the last 6 months) * HIV infection, by screening and confirmatory assays * Hepatitis C virus (HCV) infection, by screening and confirmatory assays * Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening * Any known immunodeficiency syndrome * Use of anticoagulant medications * Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 days. * Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination * Asplenia * Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination * Anticipated receipt of any investigational agent in the 28 days before or after vaccination * Has definite plans to travel to a dengue endemic area during the study * Refusal to allow storage of specimens for future research Inclusion Criteria for Second Dose of Vaccine: * Good general health as determined by physical examination and review of medical history * Available for the duration of the study, approximately 26 weeks after second dose * Ongoing willingness to continue to participate in the study * Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of vaccine-related adverse events (AEs), graded by severity | Measured through Day 540 | — |
| Measurement of neutralizing antibody titers to DEN1, DEN2, DEN3, and DEN4 at Day 0 and 28, 56, and 90 days after each vaccination | Measured at Day 0 and 28, 56, and 90 days after each vaccination | Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates will be determined at Day 0 and 28, 56, and 90 days after each vaccination. |
| Determination if a second dose of vaccine given at Day 360 will induce seropositivity in those vaccinees who remained seronegative to one or more DENV serotypes following the first vaccination | Measured through Day 540 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency, quantity, and duration of viremia following each vaccination | Measured through Day 540 | — |
| Greater than or equal to 4-fold rise in serum neutralizing antibody titer by Day 450 compared with Day 360 | Measured at Day 450 | — |
| Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4 | Measured through Day 540 | Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by seropositivity to DEN virus (PRNT50 greater than or equal to 1:10). • Seropositivity will be defined as: PRNT50 to DEN1, DEN2, DEN3, DEN4 greater than or equal to 1:10 by Day 90 post-each vaccination |
| Duration of the antibody response in recipients of the tetravalent vaccine | Measured through Day 540 | The PRNT50 to DEN1, DEN2, DEN3, and DEN4 will be determined for all specimens collected at Day 180 post-each vaccination. |
Countries
United States
Outcome results
None listed