Safety of and Immune Response of a 2-dose Regimen of rDEN1delta30 Dengue Virus Vaccine

Study Overview
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Brief Summary
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Dengue fever, 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 of and immune response to a 2-dose regimen of a new monovalent dengue virus vaccine. This study will test the dengue virus vaccine DEN1delta30 in healthy adults.

Detailed Description
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Dengue viruses account for more than 50 million cases of dengue fever and one half million cases annually of dengue hemorrhagic fever/shock syndrome. Dengue virus infections can cause illness ranging from mild, self-limited febrile illness to life threatening diseases. The goal of dengue vaccine development is to induce a long-lived antibody response against all four dengue serotypes. The rDEN1delta30 vaccine is a live attenuated dengue virus vaccine that may be protective against dengue serotype 1 (DEN1). The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a 2-dose regimen of rDEN1delta30 dengue virus vaccine. The regimen will differ in when the second booster shot of the vaccine is given. This study will last 162 days (about 23 weeks) for those participants in Cohort 1, and 222 days (about 32 weeks) for those in Cohort 2. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 120. Participants in Cohort 2 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 180. There will be a total of 25 visits for each cohort. For both cohorts, the first and second vaccination days will include a physical exam and blood and urine collection, vital signs measurements, and receipt of the vaccine. A 30 minute observation period will follow vaccination. Participants will take their temperature at home three times a day for the first 16 days and report it in a diary. At all other study visits, vital signs measurements, a physical exam, and blood and/or urine collection will occur. At selected study visits, participants will turn in their diary cards. Some participants may be asked to join an optional skin biopsy substudy.

Official Title
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Safety and Immunogenicity of a 2-Dose Regimen of rDEN1delta30 Dengue Serotype 1 Vaccine With Boosting at 4 Versus 6 Months

Conditions
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Dengue

Intervention / Treatment
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* Biological: rDEN1delta30
* 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 (23 weeks for Cohort 1 and 32 weeks for Cohort 2) Willing to use acceptable forms of contraception for the duration of the study 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 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 infected Hepatitis C virus (HCV) infected Hepatitis B surface antigen positive Known immunodeficiency syndrome Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Individuals using topical or nasal corticosteroids are not excluded. Previous receipt of a live vaccine within 4 weeks prior to study entry Previous receipt of a killed vaccine within 2 weeks prior to study entry Absence of spleen Previous receipt of blood products within 6 months prior to study entry Previous receipt of dengue virus or other flavivirus (e.g., yellow fever virus, St.Louis encephalitis, West Nile virus) infection Previous receipt of yellow fever or dengue vaccine Plans to travel to an area where dengue infection is common Previous receipt of any 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>Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 120. | Biological: rDEN1delta30<br>* Live attenuated rDEN1delta30 vaccine at a dose of 10^3 PFU<br>|
| Experimental: 2<br>Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 180. | Biological: rDEN1delta30<br>* Live attenuated rDEN1delta30 vaccine at a dose of 10^3 PFU<br>|
| Placebo Comparator: 3<br>Two subcutaneous vaccinations with placebo into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on either Day 120 or 180, depending on arm assignment. | Biological: Placebo<br>* Placebo for rDEN1delta30<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and immunogenicity of a two-dose regimen of the rDEN1delta30 vaccine given as two doses separated by four or six months |  | Throughout study | 
| To determine the optimum interval between first and second dose of rDEN1delta30 vaccine, as assessed by neutralizing antibody response to DEN1 induced by the vaccine |  | At 4 and 6 weeks after first and second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the frequency, quantity, and duration of viremia following each vaccine dose, based on the mean peak viremia, mean day of onset, and mean duration of viremia |  | Throughout study | 
| To determine the number of vaccinees infected with rDEN1delta30 virus |  | Throughout study | 
| To compare the infectivity rates, safety, and immunogenicity between dose 1 and 2 within a cohort and between cohorts |  | Throughout study | 
| To evaluate the immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy |  | Throughout study | 
| To evaluate the phenotype and activation of peripheral blood mononuclear cells (PBMCs) at primary infection and challenge with DEN1 |  | 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