Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults - Full Text View

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: rDEN4delta30-200,201 Biological: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
Official Title:	Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-200,201, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

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:

Frequency of vaccine-related adverse events, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42 [ Time Frame: At 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Durability of antibody responses to DEN4 virus [ Time Frame: At 180 days ] [ Designated as safety issue: No ]
Frequency, quantity, and duration of viremia in each dose cohort [ Time Frame: Thoughout study ] [ Designated as safety issue: No ]
Number of vaccinees infected with vaccine virus in each dose cohort [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Duration of antibody response determined by serum neutralizing antibody [ Time Frame: At 180 days ] [ Designated as safety issue: No ]
Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Compare infectivity rates, safety, and immunogenicity between dose cohorts [ Time Frame: At study completion ] [ Designated as safety issue: Yes ]
Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment:	56
Study Start Date:	June 2006
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm.	Biological: rDEN4delta30-200,201 Live attenuated dengue 4 vaccine (one of three doses)
Experimental: 2 One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1.	Biological: rDEN4delta30-200,201 Live attenuated dengue 4 vaccine (one of three doses)
Experimental: 3 One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2.	Biological: rDEN4delta30-200,201 Live attenuated dengue 4 vaccine (one of three doses)
Placebo Comparator: 4 One subcutaneous vaccination with placebo into the deltoid region of either arm.	Biological: Placebo Placebo for rDEN4delta30-200,201

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 rDEN4delta30-200,201. 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.

This study will last 180 days. There will be three cohorts in this dose de-escalation study. Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30-200,201 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 lower dose of rDEN4delta30-200,201 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the lowest dose of rDEN4delta30-200,201 or placebo.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days. Study visits will occur 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
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, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study
Laboratory abnormalities at study screening
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
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 virus, 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: NCT00270699

Locations

United States, Maryland
Center for Immunization Research, Johns Hopkins School of Public Health
Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Johns Hopkins Bloomberg School of Public Health

Investigators

Principal Investigator:

Anna Durbin, MD

Center for Immunization Research, Johns Hopkins School of Public Health

More Information

Publications:

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.

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

Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J. 2004 Oct;80(948):588-601. Review.

Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. Review.

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.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00270699 History of Changes
Other Study ID Numbers:	CIR 214, WIRB Protocol Number 2006478
Study First Received:	December 27, 2005
Last Updated:	December 31, 2012
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

Additional relevant MeSH terms:

Dengue
Dengue Hemorrhagic Fever
Fever
Arbovirus Infections
Virus Diseases
Flavivirus Infections

Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Body Temperature Changes
Signs and Symptoms

ClinicalTrials.gov processed this record on May 21, 2013