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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Center for Immunization Research
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00094705

Purpose

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.

Condition	Intervention	Phase
Dengue Fever	Biological: rDEN2/4delta30(ME) Vaccine Biological: Placebo	Phase I

MedlinePlus related topics: Dengue Fever Hemorrhagic Fevers

U.S. FDA Resources

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

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

Primary Outcome Measures:

Frequency and severity of vaccine-related adverse effects for each dose graded by severity [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Amount of dengue 2 neutralizing antibody induced by the vaccine [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the durability of the antibody response out to Day 180 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To assess the frequency, quantity, and duration of viremia in each dose cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To determine the number of vaccinees infected with rDEN2/4delta30(ME) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups [ Time Frame: At study completion ] [ Designated as safety issue: No ]
To 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 ]

Enrollment:	28
Study Start Date:	January 2005
Study Completion Date:	April 2006
Primary Completion Date:	April 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental One subcutaneous vaccination with a 10^3 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.	Biological: rDEN2/4delta30(ME) Vaccine Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)
2: Experimental One subcutaneous vaccination with a 10^5 PFU dose of rDEN2/4delta30(ME) vaccine given in the deltoid region of either arm.	Biological: rDEN2/4delta30(ME) Vaccine Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)
3: Placebo Comparator One subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm.	Biological: Placebo Placebo for rDEN2/4delta30(ME) vaccine

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094705

Locations

United States, Maryland
Johns Hopkins School of Public Health
Baltimore, Maryland, United States, 21205

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:

Edelman R. Dengue and dengue vaccines. J Infect Dis. 2005 Mar 1;191(5):650-3. Epub 2005 Jan 27. No abstract available.

Guzman MG, Mune M, Kouri G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. Review.

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.

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.

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.

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Anna Durbin, MD )
Study ID Numbers:	CIR 189, H.22.03.09.26.A2
Study First Received:	October 21, 2004
Last Updated:	January 18, 2008
ClinicalTrials.gov Identifier:	NCT00094705
Health Authority:	United States: Food and Drug Administration

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

Dengue Vaccine
Dengue Virus
Dengue Hemorrhagic Fever
Dengue Shock Syndrome

Study placed in the following topic categories:

Virus Diseases
Fever
Hemorrhagic Fevers, Viral
Shock
Dengue
Hemorrhagic fever

Viral hemorrhagic fever
Dengue fever
Healthy
Arbovirus Infections
Dengue Hemorrhagic Fever

Additional relevant MeSH terms:

RNA Virus Infections
Flaviviridae Infections
Flavivirus Infections

ClinicalTrials.gov processed this record on January 16, 2009