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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults

Primary Purpose

Dengue Fever

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN4delta30-200,201
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue Fever focused on measuring Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Center for Immunization Research, Johns Hopkins School of Public Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

4

Arm Description

One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm.

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.

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.

One subcutaneous vaccination with placebo into the deltoid region of either arm.

Outcomes

Primary Outcome Measures

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
Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42

Secondary Outcome Measures

Durability of antibody responses to DEN4 virus
Frequency, quantity, and duration of viremia in each dose cohort
Number of vaccinees infected with vaccine virus in each dose cohort
Duration of antibody response determined by serum neutralizing antibody
Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy
Compare infectivity rates, safety, and immunogenicity between dose cohorts
Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy

Full Information

First Posted
December 27, 2005
Last Updated
December 31, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Johns Hopkins Bloomberg School of Public Health
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1. Study Identification

Unique Protocol Identification Number
NCT00270699
Brief Title
Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Johns Hopkins Bloomberg School of Public Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Fever
Keywords
Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm.
Arm Title
2
Arm Type
Experimental
Arm Description
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.
Arm Title
3
Arm Type
Experimental
Arm Description
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.
Arm Title
4
Arm Type
Placebo Comparator
Arm Description
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Intervention Type
Biological
Intervention Name(s)
rDEN4delta30-200,201
Intervention Description
Live attenuated dengue 4 vaccine (one of three doses)
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo for rDEN4delta30-200,201
Primary Outcome Measure Information:
Title
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
Title
Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42
Time Frame
At 42 days
Secondary Outcome Measure Information:
Title
Durability of antibody responses to DEN4 virus
Time Frame
At 180 days
Title
Frequency, quantity, and duration of viremia in each dose cohort
Time Frame
Thoughout study
Title
Number of vaccinees infected with vaccine virus in each dose cohort
Time Frame
Throughout study
Title
Duration of antibody response determined by serum neutralizing antibody
Time Frame
At 180 days
Title
Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy
Time Frame
Throughout study
Title
Compare infectivity rates, safety, and immunogenicity between dose cohorts
Time Frame
At study completion
Title
Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy
Time Frame
Throughout study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Durbin, MD
Organizational Affiliation
Center for Immunization Research, Johns Hopkins School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Immunization Research, Johns Hopkins School of Public Health
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15688284
Citation
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.
Results Reference
background
PubMed Identifier
15566333
Citation
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.
Results Reference
background
PubMed Identifier
15466994
Citation
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.
Results Reference
background
PubMed Identifier
15057297
Citation
Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. doi: 10.1172/JCI21512.
Results Reference
background
PubMed Identifier
14740952
Citation
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.
Results Reference
background

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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults

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