Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3-3'Ddelta30) in Healthy Adults - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00712803

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 evaluate the safety of and immune response to a new dengue virus vaccine in healthy adults.

Condition	Intervention	Phase
Dengue	Biological: rDEN3-3'D4delta30	Phase I

MedlinePlus related topics: Dengue Fever

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase I Dose Comparison Study of the Safety and Immunogenicity of rDEN3-3'Ddelta30, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3

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

Primary Outcome Measures:

Safety and immunogenicity, as assessed by neutralizing antibody titers [ Time Frame: At 4 weeks and 6 weeks after vaccination ] [ Designated as safety issue: Yes ]
Frequency of vaccine related adverse events as graded by severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Frequency, quantity, and duration of viremia after a single dose of vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Number of vaccines infected with rDEN3-3'D4delta30 [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Infectivity rates, safety, and immunogenicity of a single dose of rDEN3-3'D4delta30 vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Durability of antibody response [ Time Frame: At 26 Weeks after vaccination ] [ Designated as safety issue: No ]
Obtain an estimate for the Human Infectious Dose-50% (HID50) idf dose dependent infectivity is observed [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:

56

Arms	Assigned Interventions
1: Experimental One subcutaneous vaccination (10^3 dose of vaccine) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm.	Biological: rDEN3-3'D4delta30 Live attenuated 10^3 dose of rDEN3-3'D4delta30 vaccine.
2: Experimental One subcutaneous vaccination (10^5 dose of vaccine or placebo) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm OR one subcutaneous vaccination (10^1 dose of vaccine or placebo) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm.	Biological: rDEN3-3'D4delta30 Live attenuated 10^5 dose of rDEN3-3'D4delta30 vaccine. Biological: rDEN3-3'D4delta30 Live attenuated 10^1 dose of rDEN3-3'D4delta30 vaccine.

Detailed Description:

Dengue viruses cause dengue fever and 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 rDEN3-3'D4delta30. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults.

There will be two groups in this study. Participants in Group 1 will be randomly assigned to receive rDEN3-3'D4delta30 vaccine or placebo at study entry. The dosing for Group 2 will be determined by a safety review of all participants in Group 1. If less than 90 % of the Group 1 participants seroconvert to DEN3 participants in Group 2 will receive a higher dose of rDEN3-3'D4delta30. If at least 90 % of Group 1 participants seroconvert to DEN3, participants in Group 2 will receive a lower dose of rDEN3-3'D4delta30.

All participants will be required to monitor their temperature three times each day for the first 16 days following each vaccination. Study visits will occur 30 minutes following each vaccination and every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, 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
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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. More information on this criterion can be found in the protocol.
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00712803

Locations

United States, District of Columbia

Washington, District of Columbia, United States, 20037
United States, Maryland
Center for Immunization Research, Johns Hopkins University of Public Health
Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

Anna Durbin, MD

Center for Immunization Research (CIR), Johns Hopkins School of Public Health

More Information

Publications:

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.

Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52. Review.

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

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Anna Durbin, MD )
Study ID Numbers:	CIR 252
Study First Received:	July 8, 2008
Last Updated:	July 8, 2008
ClinicalTrials.gov Identifier:	NCT00712803
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Fever
Virus Diseases
Hemorrhagic Fevers, Viral
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 14, 2009