Safety of and Immune Response to a Dengue Virus Vaccine (rDEN2/4delta30[ME]) 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, as well as 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 rDEN2/4delta30(ME), which is derived from the DEN2 and DEN4 serotypes. This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive rDEN2/4delta30(ME) 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 higher dose of rDEN2/4delta30(ME) or placebo. After vaccination, participants will be observed for at least 30 minutes for immediate adverse reactions. Participants will also be asked to monitor their temperature every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by 4 additional visits at selected days through Day 180. Blood collection 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 rDEN2/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 2

Conditions
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Dengue Fever

Intervention / Treatment
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* Biological: rDEN2/4delta30(ME) Vaccine
* 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, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study Hematologic disease 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 Participation in another investigational vaccine or drug trial within 60 days of starting this study, or while this trial is ongoing 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, 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 a 10^3 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm. | Biological: rDEN2/4delta30(ME) Vaccine<br>* Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)<br>|
| Experimental: 2<br>One subcutaneous vaccination with a 10^5 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm. | Biological: rDEN2/4delta30(ME) Vaccine<br>* Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)<br>|
| Placebo Comparator: 3<br>One subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm. | Biological: Placebo<br>* Placebo for rDEN2/4delta30(ME) vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of vaccine-related adverse effects for each dose graded by severity |  | Throughout study | 
| Amount of dengue 2 neutralizing antibody induced by the vaccine |  | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the durability of the antibody response out to Day 180 |  | Throughout study | 
| To assess the frequency, quantity, and duration of viremia in each dose cohort studied |  | Throughout study | 
| To determine the number of vaccinees infected with rDEN2/4delta30(ME) |  | Throughout study | 
| To compare the T cell mediated immune response against dengue viruses of those volunteers infected with the rDEN2/4delta30(ME) vaccine virus with that of uninfected volunteers and placebo recipients |  | Throughout study | 
| If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups |  | At study completion | 
| To 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 Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome