Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) in Healthy Adults

National Institute of Allergy and Infectious Diseases (NIAID)84 enrolled

Overview

Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.

Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults. This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort. After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

Conditions

Dengue

Interventions

rDEN4delta30-4995BIOLOGICAL

Live attenuated rDEN4delta30-4995 vaccine (one of three doses)

PlaceboBIOLOGICAL

Placebo for rDEN4delta30-4995

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adult males and non-pregnant females between 18 and 50 years of age * Good general health * Available for the duration of the study * Willing to use acceptable methods of contraception for the duration of the study Exclusion Criteria: * Significant neurologic, cardiac, lung, liver, rheumatologic, autoimmune, or kidney disease * Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study * Significant laboratory abnormalities * Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry * History of severe allergic reaction or anaphylaxis * Severe asthma * HIV-1 serotype infected * Hepatitis C virus (HCV) infected * Hepatitis B surface antigen positive * Immunodeficiency syndrome * Use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. Individuals using topical or nasal corticosteroids are not excluded. * Live vaccine within 4 weeks prior to study entry * Killed vaccine within 2 weeks prior to study entry * Absence of spleen * Blood products within 6 months prior to study entry * Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection * Prior receipt of yellow fever or dengue vaccine (licensed or experimental) * Plans to travel to an area where dengue infection is common * Received an investigational agent within 30 days prior to study entry * Other condition that, in the opinion of the investigator, would affect participation in the study * Pregnant or breastfeeding

Locations (1)

Vanderbilt University School of Medicine

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Frequency of vaccine-related adverse events, graded by severity for each dose

Time frame: Throughout study

Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)

Time frame: At Days 28 and 42

Secondary Outcomes

Durability of antibody responses to DEN4 virus

Time frame: At Month 6

Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort

Time frame: Throughout study

Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine

Time frame: Throughout study

Data from ClinicalTrials.gov

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