Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults

National Institute of Allergy and Infectious Diseases (NIAID)56 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 test the safety of and immune response to a new dengue virus vaccine in healthy adults.

Dengue viruses cause dengue fever and the more severe dengue hemorrhagic fever/shock syndrome. More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection, which is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live attenuated dengue virus vaccine called rDEN4delta30-200,201. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults. This study will last 180 days. There will be three cohorts in this dose de-escalation study. Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30-200,201 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a lower dose of rDEN4delta30-200,201 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the lowest dose of rDEN4delta30-200,201 or placebo. After vaccination, participants will be asked to monitor their temperatures every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, and a targeted physical exam will occur at each study visit. Some participants will 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 Fever

Interventions

rDEN4delta30-200,201BIOLOGICAL

Live attenuated dengue 4 vaccine (one of three doses)

PlaceboBIOLOGICAL

Placebo for rDEN4delta30-200,201

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: * Willing to be followed for the duration of the study * Willing to use acceptable methods of contraception * Good general health Exclusion Criteria: * Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease * Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study * Laboratory abnormalities at study screening * Alcohol or drug abuse within 12 months prior to study entry * History of severe allergic reaction or anaphylaxis * Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry * HIV-1 infected * Hepatitis C virus infected * Hepatitis B surface antigen positive * Known immunodeficiency syndrome * Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used 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 * Blood products within 6 months prior to study entry * Previously received a licensed or experimental yellow fever or dengue vaccine * Surgical removal of spleen * History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus, Japanese encephalitis virus) * Other condition that, in the opinion of the investigator, would affect the participant's participation in the study * Plan to travel to an area where dengue infection is common * Pregnancy or breastfeeding

Locations (1)

Center for Immunization Research, Johns Hopkins School of Public Health

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Frequency of vaccine-related adverse events, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions

Time frame: Throughout study

Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42

Time frame: At 42 days

Secondary Outcomes

Durability of antibody responses to DEN4 virus

Time frame: At 180 days

Frequency, quantity, and duration of viremia in each dose cohort

Time frame: Thoughout study

Number of vaccinees infected with vaccine virus in each dose cohort

Time frame: Throughout study

Duration of antibody response determined by serum neutralizing antibody

Time frame: At 180 days

Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy

Time frame: Throughout study

Compare infectivity rates, safety, and immunogenicity between dose cohorts

Time frame: At study completion

Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy

Time frame: Throughout study

Data from ClinicalTrials.gov

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