Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) 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 evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.

Detailed Description
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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.

Official Title
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Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

Conditions
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Dengue

Intervention / Treatment
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* Biological: rDEN4delta30-4995
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

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 rDEN4delta30-4995 vaccine (10^5 PFU dose) into the deltoid region of either arm. | Biological: rDEN4delta30-4995<br>* Live attenuated rDEN4delta30-4995 vaccine (one of three doses)<br>|
| Experimental: 2<br>One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1. | Biological: rDEN4delta30-4995<br>* Live attenuated rDEN4delta30-4995 vaccine (one of three doses)<br>|
| Experimental: 3<br>One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2. | Biological: rDEN4delta30-4995<br>* Live attenuated rDEN4delta30-4995 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 rDEN4delta30-4995<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, graded by severity for each dose |  | Throughout study | 
| Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT) |  | At Days 28 and 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of antibody responses to DEN4 virus |  | 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 |  | Throughout study | 
| Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine |  | Throughout study | 

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