A Phase I Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Tetravalent Recombinant Subunit Dengue Vaccine (V180) in Healthy Adults Who Previously Received a Live-Attenuated Tetravalent Vaccine (TV003 or TV005)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Dengue
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 20
- Locations
- 3
- Primary Endpoint
- Virus neutralizing antibody levels, as measured by the PRNT with a 50% neutralization cutoff (PRNT50 titer)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
Dengue viruses are mosquito-borne flaviviruses. Each year, dengue viruses infect millions of people throughout the tropics and subtropics. This study will evaluate the safety, tolerability, and immunogenicity of a tetravalent recombinant subunit dengue vaccine (V180) in healthy adults who previously received a live-attenuated tetravalent dengue vaccine (TV003 or TV005).
Detailed Description
Dengue fever is caused by any one of four viral serotypes (DENV1, DENV2, DENV3, and DENV4) and infection by any serotype creates life-long immunity against that serotype. V180 is an experimental tetravalent recombinant subunit dengue vaccine that would protect against all four serotypes (DENV1, DENV2, DENV3, and DENV4). The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of adjuvanted (with Alhydrogel™) and nonadjuvanted formulations of V180 in healthy adults who have previously received the live-attenuated tetravalent dengue vaccine TV003 or TV005. Participants will be randomly assigned to receive one intramuscular injection of either adjuvanted V180, nonadjuvanted V180, or placebo at study entry (Day 1). Participants will record their temperature and any adverse events for 14 days after receiving the vaccination. Additional study visits will occur on Days 15, 28 and 180. Visits will include a physical examination and blood and urine collection. Study staff will contact participants by telephone at Days 7 and 90 (and at other occasional time points between Days 90 and 180) for health and safety follow-up monitoring.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult male or female between 18 and 50 years of age, inclusive
- •Has previously received TV003 or TV005 live-attenuated tetravalent vaccine (LATV) DENV vaccine, successfully completed the study with no safety concerns, and seroconverted to 3 or more serotypes
- •Good general health as determined by physical examination, laboratory screening, and review of medical history
- •Willingness to participate in the study as evidenced by signing the informed consent document
- •Willingness to complete all scheduled visits and to comply with the study procedures
- •Available for the duration of the study, approximately 26 weeks post-vaccination
- •Ability to read, understand, and complete study questionnaires (i.e., the Vaccination Report Card)
- •Has access to a telephone
- •Is afebrile (less than 100.4°F \[less than 38.0°C\] oral or equivalent) for 72 hours prior to vaccination. Note: If a participant is not afebrile for 72 hours prior to vaccination, vaccination can be deferred if all other eligibility criteria are met and time allows for vaccination.
- •Females Only: Female participants of childbearing potential 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 (6 months or longer since last sexual encounter). All female participants will be considered having childbearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.
Exclusion Criteria
- •Is pregnant or breastfeeding, or expecting to conceive at any time from signing the informed consent through Day 180 after receiving the study vaccine/placebo
- •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
- •Has 1 or more of the following screening laboratory values:
- •Alanine aminotransferase (ALT) greater than or equal to 1.25 times the upper limit of normal (ULN)
- •Positive urine glucose or urine protein greater than 1+ by dipstick or urinalysis
- •Serum creatinine greater than ULN by gender
- •Hematology results as follows:
- •Hemoglobin meeting Grade 1 or higher criteria
- •Absolute neutrophil count (ANC) less than 1,000/mm\^3
Outcomes
Primary Outcomes
Virus neutralizing antibody levels, as measured by the PRNT with a 50% neutralization cutoff (PRNT50 titer)
Time Frame: Measured at Day 28