Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults

Study Overview
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Brief Summary
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Dengue fever, caused by dengue viruses, is a major health problem in the 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, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults. This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo. After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.

Official Title
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Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3

Conditions
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Dengue

Intervention / Treatment
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* Biological: rDEN3/4delta30(ME)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good general health Available for the duration of the study Willing to use acceptable forms of contraception for the duration of the study Exclusion Criteria: Significant neurologic, heart, 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 Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry HIV-1 infected Hepatitis C virus (HCV) infected Hepatitis B surface antigen positive Immunodeficiency syndrome Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants 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 Previously received yellow fever or dengue vaccine 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 interfere with the study 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 rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm. | Biological: rDEN3/4delta30(ME)<br>* Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)<br>|
| Experimental: 2<br>One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. | Biological: rDEN3/4delta30(ME)<br>* Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)<br>|
| Experimental: 3<br>One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. | Biological: rDEN3/4delta30(ME)<br>* Live attenuated rDEN3/4delta30(ME) 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 rDEN3/4delta30(ME)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance |  | Throughout study | 
| Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180 |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the frequency, quantity, and duration of viremia in each dose cohort studied |  | Throughout study | 
| Determine the number of vaccinees infected with rDEN3/4delta30(ME) |  | Throughout study | 
| Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy |  | Throughout study | 
| Compare the infectivity rates, safety, and immunogenicity between dose groups |  | At study completion | 
| Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are 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 Fever, Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome