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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-200,201, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

Conditions
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Dengue Fever

Intervention / Treatment
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* Biological: rDEN4delta30-200,201
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm. | Biological: rDEN4delta30-200,201<br>* Live attenuated dengue 4 vaccine (one of three doses)<br>|
| Experimental: 2<br>One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1. | Biological: rDEN4delta30-200,201<br>* Live attenuated dengue 4 vaccine (one of three doses)<br>|
| Experimental: 3<br>One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2. | Biological: rDEN4delta30-200,201<br>* Live attenuated dengue 4 vaccine (one of three doses)<br>|
| Placebo Comparator: 4<br>One subcutaneous vaccination with placebo into the deltoid region of either arm. | Biological: Placebo<br>* Placebo for rDEN4delta30-200,201<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Throughout study | 
| Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42 |  | At 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of antibody responses to DEN4 virus |  | At 180 days | 
| Frequency, quantity, and duration of viremia in each dose cohort |  | Thoughout study | 
| Number of vaccinees infected with vaccine virus in each dose cohort |  | Throughout study | 
| Duration of antibody response determined by serum neutralizing antibody |  | At 180 days | 
| Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy |  | Throughout study | 
| Compare infectivity rates, safety, and immunogenicity between dose cohorts |  | At study completion | 
| Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome