Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus

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 subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. The purpose of this study is to determine the safety and immune response to a vaccine containing a particular dengue serotype when an individual has been previously vaccinated with a different dengue serotype.

Detailed Description
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The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype. This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo. Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.

Official Title
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Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals

Conditions
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Dengue Hemorrhagic Fever

Intervention / Treatment
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* Biological: rDEN1delta30
* Biological: rDEN2/4delta30(ME)
* Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous vaccination with rDEN1delta30, rDEN2/4delta30(ME), OR rDEN4delta30 vaccine General good health Available for the duration of the study Willing to use accepted forms of contraception Exclusion Criteria: Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study Certain abnormal laboratory values Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry History of severe allergy or anaphylaxis Severe asthma requiring an emergency room visit or hospitalization within 6 months of study entry HIV infected Hepatitis C virus infected Hepatitis B surface antibody positive Known immunodeficiency syndrome Use of corticosteroids or immunosuppressive drugs 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded. Receipt of live vaccine within 4 weeks of study entry Receipt of killed vaccine within 2 weeks of study entry Absence of spleen Plan to travel to an area where dengue virus is common Any investigational product within 30 days of 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>Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. | Biological: rDEN1delta30<br>* Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.<br>|
| Experimental: 2<br>Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) into the deltoid region of either arm. | Biological: rDEN2/4delta30(ME)<br>* Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.<br>|
| Experimental: 3<br>Participants previously vaccinated with rDEN2/4delta30(ME) will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. | Biological: rDEN1delta30<br>* Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.<br>|
| Experimental: 4<br>Participants previously vaccinated with rDEN1delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) vaccine into the deltoid region of either arm. | Biological: rDEN2/4delta30(ME)<br>* Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.<br>|
| Placebo Comparator: 5<br>One subcutaneous vaccination with placebo into the deltoid region of either arm. | Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME)<br>* Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance |  | Throughout study | 
| Neutralizing antibody to all four dengue serotypes |  | At Days 0, 28, and 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied |  | Throughout study | 
| To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype |  | Throughout study | 
| Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort |  | At study completion | 
| Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy |  | Throughout study | 
| Characterize the antibody response after heterolouous vaccine infection |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue Fever, Dengue Hemorrhagic Fever, Dengue Vaccination