Dengue
Conditions
Brief summary
The purpose of this study is to evaluate the ability of a single dose of a live attenuated recombinant tetravalent dengue vaccine (TetraVax-DV-TV003, referred to as TV003) to protect against infection with a controlled human infection strain of either DENV-2 (rDEN2Δ30-7169) or DENV-3 (rDEN3Δ30) in adults 18 to 50 years of age with no history of previous flavivirus infection.
Detailed description
This study will evaluate the ability of a single dose of a live attenuated recombinant tetravalent dengue vaccine (TetraVax-DV-TV003, referred to as TV003) to protect against infection with a controlled human infection strain of either DENV-2 (rDEN2Δ30-7169) or DENV-3 (rDEN3Δ30) in adults 18 to 50 years of age with no history of previous flavivirus infection. Participants will be randomly assigned to receive either TV003 or placebo at study entry (Day 0) and either rDEN2Δ30-7169 or rDEN3Δ30 on Day 28. Study visits will occur on Days 0, 4, 6, 8, 10, 12, 14, 16, 21, 28, 32, 34, 36, 38, 40, 42, 44, 49, 56, 84, 118, and 208. Visits may include a physical examination and blood collection.
Interventions
BIOLOGICALTetraVax-DV-TV003 (TV003)
TV003 contains 10\^3.3 plaque-forming units (PFU)/mL of rDEN1Δ30, 10\^3.3 PFU/mL of rDEN2/4Δ30(ME), 10\^3.3 PFU/mL of rDEN3Δ30/31-7164, and 10\^3.3 PFU/mL of rDEN4Δ30. Administered by subcutaneous injection in the deltoid region of the upper arm
BIOLOGICALrDEN2Δ30-7169 (DENV-2)
Administered at a dose of 10\^3 PFU by subcutaneous injection in the deltoid region of the upper arm
BIOLOGICALrDEN3Δ30 (DENV-3)
Administered at a dose of 10\^3 PFU by subcutaneous injection in the deltoid region of the upper arm
BIOLOGICALPlacebo
Administered by subcutaneous injection in the 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
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult male or female between 18 and 50 years of age, inclusive. * Good general health as determined by physical examination, laboratory screening, and review of medical history. * Available for the duration of the study, which is approximately 28 weeks. * Willingness to participate in the study as evidenced by signing the informed consent document. * Females only: Female subjects of childbearing potential should be willing to use effective contraception and have no plans to undergo IVF (in vitro fertilization) during participation in the trial. Reliable methods of contraception include hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (greater than or equal to 6 months since last sexual encounter with a male). All female subjects will be considered as having childbearing potential, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.
Exclusion criteria
* Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, or breast-feeding. * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies. * Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability 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 subject participating in the trial, or would render the subject 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 subject history. * History of a severe allergic reaction or anaphylaxis. * Severe asthma (emergency room visit or hospitalization within the last 6 months). * HIV infection, as indicated by screening and confirmatory assays. * Hepatitis C virus (HCV) infection, as indicated by screening and confirmatory assays. * Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) screening. * Any known immunodeficiency syndrome. * Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications). * Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a 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 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. * History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis Encephalitis virus, or West Nile virus). Subjects will also be screened for Zika virus if they have traveled to areas of South and Central America in the past 18 months that have reported Zika-virus transmission (per the Centers for Disease Control and Prevention Zika travel information). * Previous receipt of a flavivirus vaccine (licensed or experimental). * Anticipated receipt of any investigational agent in the 28 days before or after vaccination. * Definite plans to travel to a dengue-endemic area during the study. * Refusal to allow specimen storage for future research. Inclusion Criteria for Challenge with rDEN2Δ30-7169 or rDEN3Δ30 * Currently enrolled in the study. * Good general health as determined by physical examination and review of medical history. * Available for the duration of the study, which is approximately 24 weeks after challenge. * Willingness to participate in the study as evidenced by signing the informed consent document. * Females only: Female subjects of childbearing potential should be willing to use effective contraception for the duration of the trial. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (greater than or equal to 6 months since last sexual encounter). All female subjects will be considered as having childbearing potential, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or who are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of serious adverse events (SAEs) | Measured through Day 208 | Evaluated using the Adverse Event Grading Table in the study protocol |
| Frequency of rDEN3Δ30 viremia | Measured through Month 1 | Based on statistical analysis of laboratory evaluations |
| Occurrence of solicited local and general adverse events (AEs) | Measured through Day 56 | Evaluated using the Adverse Event Grading Table in the study protocol |
| Occurrence of unsolicited AEs | Measured through Day 56 | Evaluated using the Adverse Event Grading Table in the study protocol |
| Frequency of rDEN2Δ30-7160 viremia | Measured through Month 1 | Based on statistical analysis of laboratory evaluations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of TV003 recipients infected with vaccine virus DENV-1, DENV-2, DENV-3, and DENV-4 | Measured through Day 208 | As defined by recovery of vaccine virus from the blood or serum of a subject and/or seropositivity OR seroconversion to DENV |
| Serum plaque reduction neutralization titer 50% (PRNT50) to DENV-1, DENV-2, DENV-3, and DENV-4 viruses | Measured through Day 180 | Determined by seropositivity and seroconversion frequencies |
| Frequency of viremia after vaccination with TV003 | Measured through Day 208 | Based on statistical analysis of laboratory evaluations |
Countries
United States
Outcome results
None listed