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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Center for Immunization Research
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00375726

Purpose

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.

Condition	Intervention	Phase
Dengue	Biological: rDEN3/4delta30(ME) Biological: Placebo	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Dengue Fever Hemorrhagic Fevers

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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 [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assess the frequency, quantity, and duration of viremia in each dose cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Determine the number of vaccinees infected with rDEN3/4delta30(ME) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Compare the infectivity rates, safety, and immunogenicity between dose groups [ Time Frame: At study completion ] [ Designated as safety issue: No ]
Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	84
Study Start Date:	October 2006
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm.	Biological: rDEN3/4delta30(ME) Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
2: Experimental 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.	Biological: rDEN3/4delta30(ME) Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
3: Experimental 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.	Biological: rDEN3/4delta30(ME) Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
4: Placebo Comparator One subcutaneous vaccination with placebo into the deltoid region of either arm.	Biological: Placebo Placebo for rDEN3/4delta30(ME)

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00375726

Locations

United States, Maryland
Center for Immunization Research	Recruiting
Baltimore, Maryland, United States, 21205
Contact: Priscilla Brooks 410-955-7283 pbrooks@jhsph.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Center for Immunization Research

Investigators

Principal Investigator:

Anna Durbin, MD

Center for Immunization Research, Johns Hopkins School of Public Health

More Information

Publications:

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.

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.

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.

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. Epub 2005 Jan 27.

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Anna Durbin, MD )
Study ID Numbers:	CIR 228, WIRB Protocol Number 20061667
Study First Received:	September 12, 2006
Last Updated:	January 15, 2008
ClinicalTrials.gov Identifier:	NCT00375726 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Dengue Fever
Dengue Vaccine
Dengue Virus
Dengue Hemorrhagic Fever
Dengue Shock Syndrome

Additional relevant MeSH terms:

Virus Diseases
Hemorrhagic Fevers, Viral
RNA Virus Infections
Flaviviridae Infections

Flavivirus Infections
Dengue
Arbovirus Infections
Dengue Hemorrhagic Fever

ClinicalTrials.gov processed this record on November 09, 2009