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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults

Primary Purpose

Dengue

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN3/4delta30(ME)
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 focused on measuring Dengue Fever, Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome

Eligibility Criteria

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

Inclusion Criteria:

  • Good general health
  • Available for the duration of the study
  • Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria:

  • 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
  • Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
  • HIV-1 infected
  • Hepatitis C virus (HCV) infected
  • Hepatitis B surface antigen positive
  • Immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants using 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
  • Absence of spleen
  • Blood products within 6 months prior to study entry
  • Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection
  • Previously received yellow fever or dengue vaccine
  • Plans to travel to an area where dengue infection is common
  • Received an investigational agent within 30 days prior to 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 Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

4

Arm Description

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm.

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.

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

Outcomes

Primary Outcome Measures

Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180

Secondary Outcome Measures

Assess the frequency, quantity, and duration of viremia in each dose cohort studied
Determine the number of vaccinees infected with rDEN3/4delta30(ME)
Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy
Compare the infectivity rates, safety, and immunogenicity between dose groups
Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy

Full Information

First Posted
September 12, 2006
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
NCT00375726
Brief Title
Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults
Official Title
Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3
Study Type
Interventional

2. Study Status

Record Verification Date
December 2010
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 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, caused by dengue viruses, is a major health problem in the 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, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults. This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo. After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue
Keywords
Dengue Fever, 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
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm.
Arm Title
2
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.
Arm Title
3
Arm Type
Experimental
Arm Description
One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.
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)
rDEN3/4delta30(ME)
Intervention Description
Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo for rDEN3/4delta30(ME)
Primary Outcome Measure Information:
Title
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Time Frame
Throughout study
Title
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
Time Frame
Throughout study
Secondary Outcome Measure Information:
Title
Assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time Frame
Throughout study
Title
Determine the number of vaccinees infected with rDEN3/4delta30(ME)
Time Frame
Throughout study
Title
Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy
Time Frame
Throughout study
Title
Compare the infectivity rates, safety, and immunogenicity between dose groups
Time Frame
At study completion
Title
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: Good general health Available for the duration of the study Willing to use acceptable forms of contraception for the duration of the study Exclusion Criteria: 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 Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry HIV-1 infected Hepatitis C virus (HCV) infected Hepatitis B surface antigen positive Immunodeficiency syndrome Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants using 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 Absence of spleen Blood products within 6 months prior to study entry Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection Previously received yellow fever or dengue vaccine Plans to travel to an area where dengue infection is common Received an investigational agent within 30 days prior to 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
16553547
Citation
Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
Results Reference
background
PubMed Identifier
15642976
Citation
Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
Results Reference
background
PubMed Identifier
15827166
Citation
Blaney JE Jr, Matro JM, Murphy BR, Whitehead SS. Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys. J Virol. 2005 May;79(9):5516-28. doi: 10.1128/JVI.79.9.5516-5528.2005.
Results Reference
background
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
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Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults

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