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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN2/4delta30[ME]) in Healthy Adults

Primary Purpose

Dengue Fever

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN2/4delta30(ME) Vaccine
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, 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

Sites / Locations

  • Johns Hopkins School of Public Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

Arm Description

One subcutaneous vaccination with a 10^3 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.

One subcutaneous vaccination with a 10^5 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.

One subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm.

Outcomes

Primary Outcome Measures

Frequency and severity of vaccine-related adverse effects for each dose graded by severity
Amount of dengue 2 neutralizing antibody induced by the vaccine

Secondary Outcome Measures

To assess the durability of the antibody response out to Day 180
To assess the frequency, quantity, and duration of viremia in each dose cohort studied
To determine the number of vaccinees infected with rDEN2/4delta30(ME)
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
If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy

Full Information

First Posted
October 21, 2004
Last Updated
January 18, 2008
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
NCT00094705
Brief Title
Safety of and Immune Response to a Dengue Virus Vaccine (rDEN2/4delta30[ME]) in Healthy Adults
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2008
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
April 2006 (Actual)

3. Sponsor/Collaborators

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, 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.

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
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with a 10^3 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.
Arm Title
2
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with a 10^5 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
One subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm.
Intervention Type
Biological
Intervention Name(s)
rDEN2/4delta30(ME) Vaccine
Intervention Description
Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo for rDEN2/4delta30(ME) vaccine
Primary Outcome Measure Information:
Title
Frequency and severity of vaccine-related adverse effects for each dose graded by severity
Time Frame
Throughout study
Title
Amount of dengue 2 neutralizing antibody induced by the vaccine
Time Frame
At Day 42
Secondary Outcome Measure Information:
Title
To assess the durability of the antibody response out to Day 180
Time Frame
Throughout study
Title
To assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time Frame
Throughout study
Title
To determine the number of vaccinees infected with rDEN2/4delta30(ME)
Time Frame
Throughout study
Title
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
Time Frame
Throughout study
Title
If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups
Time Frame
At study completion
Title
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are 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, 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
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
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
15688277
Citation
Edelman R. Dengue and dengue vaccines. J Infect Dis. 2005 Mar 1;191(5):650-3. doi: 10.1086/427784. Epub 2005 Jan 27. No abstract available.
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
12139219
Citation
Sabchareon A, Lang J, Chanthavanich P, Yoksan S, Forrat R, Attanath P, Sirivichayakul C, Pengsaa K, Pojjaroen-Anant C, Chokejindachai W, Jagsudee A, Saluzzo JF, Bhamarapravati N. Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses. Am J Trop Med Hyg. 2002 Mar;66(3):264-72. doi: 10.4269/ajtmh.2002.66.264.
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
PubMed Identifier
14505913
Citation
Whitehead SS, Hanley KA, Blaney JE Jr, Gilmore LE, Elkins WR, Murphy BR. Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys. Vaccine. 2003 Oct 1;21(27-30):4307-16. doi: 10.1016/s0264-410x(03)00488-2.
Results Reference
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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN2/4delta30[ME]) in Healthy Adults

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