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

Primary Purpose

Dengue Hemorrhagic Fever

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN1delta30
rDEN2/4delta30(ME)
Placebo to rDEN1delta30 or rDEN2/4delta30(ME)
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 Hemorrhagic Fever focused on measuring Dengue Fever, Dengue Hemorrhagic Fever, Dengue Vaccination

Eligibility Criteria

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

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

Sites / Locations

  • Center for Immunization Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

4

5

Arm Description

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.

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.

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.

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.

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

Outcomes

Primary Outcome Measures

Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
Neutralizing antibody to all four dengue serotypes

Secondary Outcome Measures

Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied
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
Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort
Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy
Characterize the antibody response after heterolouous vaccine infection

Full Information

First Posted
April 6, 2007
Last Updated
December 13, 2010
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
NCT00458120
Brief Title
Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus
Official Title
Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals
Study Type
Interventional

2. Study Status

Record Verification Date
December 2010
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (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 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Hemorrhagic Fever
Keywords
Dengue Fever, Dengue Hemorrhagic Fever, Dengue Vaccination

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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.
Arm Title
2
Arm Type
Experimental
Arm Description
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.
Arm Title
3
Arm Type
Experimental
Arm Description
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.
Arm Title
4
Arm Type
Experimental
Arm Description
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.
Arm Title
5
Arm Type
Placebo Comparator
Arm Description
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Intervention Type
Biological
Intervention Name(s)
rDEN1delta30
Intervention Description
Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.
Intervention Type
Biological
Intervention Name(s)
rDEN2/4delta30(ME)
Intervention Description
Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.
Intervention Type
Biological
Intervention Name(s)
Placebo to rDEN1delta30 or rDEN2/4delta30(ME)
Intervention Description
Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME)
Primary Outcome Measure Information:
Title
Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
Time Frame
Throughout study
Title
Neutralizing antibody to all four dengue serotypes
Time Frame
At Days 0, 28, and 42
Secondary Outcome Measure Information:
Title
Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied
Time Frame
Throughout study
Title
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
Time Frame
Throughout study
Title
Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort
Time Frame
At study completion
Title
Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy
Time Frame
Throughout study
Title
Characterize the antibody response after heterolouous vaccine infection
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: 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
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
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
15937367
Citation
Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52.
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
21208923
Citation
Durbin AP, Schmidt A, Elwood D, Wanionek KA, Lovchik J, Thumar B, Murphy BR, Whitehead SS. Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic. J Infect Dis. 2011 Feb 1;203(3):327-34. doi: 10.1093/infdis/jiq059. Epub 2010 Dec 14.
Results Reference
derived

Learn more about this trial

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

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