Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults
Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-200,201, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Dengue viruses cause dengue fever and 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 rDEN4delta30-200,201. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults.
This study will last 180 days. There will be three cohorts in this dose de-escalation study. Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30-200,201 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 lower dose of rDEN4delta30-200,201 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the lowest dose of rDEN4delta30-200,201 or placebo.
After vaccination, participants will be asked to monitor their temperatures every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21205
- Center for Immunization Research, Johns Hopkins School of Public Health
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study
- Laboratory abnormalities at study screening
- 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
- 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 virus, 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: 4
One subcutaneous vaccination with placebo into the deltoid region of either arm.
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Placebo for rDEN4delta30-200,201
|
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Experimental: 1
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm.
|
Live attenuated dengue 4 vaccine (one of three doses)
|
|
Experimental: 2
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^3 PFU dose) into the deltoid region of either arm.
This arm will enroll after Arm 1.
|
Live attenuated dengue 4 vaccine (one of three doses)
|
|
Experimental: 3
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^1 PFU dose) into the deltoid region of either arm.
This arm will enroll after Arms 1 and 2.
|
Live attenuated dengue 4 vaccine (one of three doses)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Frequency of vaccine-related adverse events, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions
Time Frame: Throughout study
|
Throughout study
|
|
Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42
Time Frame: At 42 days
|
At 42 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Durability of antibody responses to DEN4 virus
Time Frame: At 180 days
|
At 180 days
|
|
Frequency, quantity, and duration of viremia in each dose cohort
Time Frame: Thoughout study
|
Thoughout study
|
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Number of vaccinees infected with vaccine virus in each dose cohort
Time Frame: Throughout study
|
Throughout study
|
|
Duration of antibody response determined by serum neutralizing antibody
Time Frame: At 180 days
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At 180 days
|
|
Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy
Time Frame: Throughout study
|
Throughout study
|
|
Compare infectivity rates, safety, and immunogenicity between dose cohorts
Time Frame: At study completion
|
At study completion
|
|
Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy
Time Frame: Throughout study
|
Throughout study
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. doi: 10.1172/JCI21512.
- Sun W, Edelman R, Kanesa-Thasan N, Eckels KH, Putnak JR, King AD, Houng HS, Tang D, Scherer JM, Hoke CH Jr, Innis BL. Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates. Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):24-31. doi: 10.4269/ajtmh.2003.69.6_suppl.0690024.
- Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA. rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers. J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.
- Guzman MG, Mune M, Kouri G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. doi: 10.1586/14789072.2.6.895.
- Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J. 2004 Oct;80(948):588-601. doi: 10.1136/pgmj.2004.019638.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CIR 214
- WIRB Protocol Number 2006478
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