Safety of and Immune Response to a West Nile Virus Vaccine (WN/DEN4-3'delta30) in Healthy Adults - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Johns Hopkins Bloomberg School of Public Health
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00094718

Purpose

West Nile (WN) virus infection is an emerging disease; WN infection may lead to paralysis, coma, and death. The purpose of this study is to test the safety of and immune response to a WN vaccine in healthy adults. The vaccine is based on a live attenuated vaccine developed against dengue virus.

Condition	Intervention	Phase
West Nile Fever Encephalitis	Biological: WN/DEN4-3'delta30 Biological: Placebo	Phase I

National Institute of Allergy and Infectious Diseases (NIAID) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety 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 West Nile/Dengue-4 3'delta30 Chimeric Virus Vaccine (WN/DEN4-3'delta30), a Live Attenuated Vaccine for West Nile Encephalitis

Resource links provided by NLM:

MedlinePlus related topics: Dengue Encephalitis Fever West Nile Virus

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 effects, graded by severity, for each dose [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Immunogenicity of vaccine against WN virus [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the durability of the antibody response [ Time Frame: At Day 180 ] [ 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 assess the immunogenicity of the WN/DEN4-3'delta30 vaccine against WN wild-type virus [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To compare the T cell medicated immune response against West Nile virus of those volunteers infected with the WN/DEN4-3'delta30 vaccine virus with that of uninfected volunteers and placebo recipients [ 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:	56
Study Start Date:	February 2005
Study Completion Date:	April 2005
Primary Completion Date:	April 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 One subcutaneous vaccination with WN/DEN4-3'delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm.	Biological: WN/DEN4-3'delta30 Live attenuated WN/DEN4-3'delta30 vaccine (one of three doses)
Experimental: 2 One subcutaneous vaccination with WN/DEN4-3'delta30 vaccine (10^4 PFU dose) into the deltoid region of either arm. This arm may enroll after the results from Arm 1 are analyzed.	Biological: WN/DEN4-3'delta30 Live attenuated WN/DEN4-3'delta30 vaccine (one of three doses)
Experimental: 3 One subcutaneous vaccination with WN/DEN4-3'delta30 vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after the results from Arm 2 are analyzed.	Biological: WN/DEN4-3'delta30 Live attenuated WN/DEN4-3'delta30 vaccine (one of three doses)
Placebo Comparator: 4 One subcutaneous vaccination with placebo vaccine into the deltoid region of either arm.	Biological: Placebo Placebo for WN/DEN4-3'delta30 vaccine

Detailed Description:

WN is widely distributed in Africa and Europe, where it is usually associated with mild illness. In the United States, WN is considered a public health threat because severe illness caused by WN infection has caused paralysis, coma, and death, especially in the elderly. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, WN/DEN4-3'delta30, which is derived from the DEN4 dengue virus and wild-type WN serotypes.

This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive the lowest dose of WN/DEN4-3'delta30 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 WN/DEN4-3'delta30 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the highest dose of WN/DEN4-3'delta30 or placebo. Immediately after receiving their injections, participants will be observed for 30 minutes for immediate adverse reactions.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days and on Day 19. Study visits will occur every other day after vaccination until Day 16, followed by 5 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
History of migraine headaches
History of encephalitis
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 of 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 participating in this study
Previously received a licensed or experimental yellow fever, tick-borne encephalitis, or dengue vaccine
Surgical removal of spleen
History of West Nile encephalitis
History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094718

Locations

United States, Maryland
Johns Hopkins School of Public Health
Baltimore, Maryland, United States, 21205
United States, Tennessee
Vanderbilt University School of Medicine
Nashville, Tennessee, United States, 37232

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:

Chang GJ, Kuno G, Purdy DE, Davis BS. Recent advancement in flavivirus vaccine development. Expert Rev Vaccines. 2004 Apr;3(2):199-220.

Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. Review.

Monath TP, McCarthy K, Bedford P, Johnson CT, Nichols R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F. Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections. Vaccine. 2002 Jan 15;20(7-8):1004-18.

Pletnev AG, Claire MS, Elkins R, Speicher J, Murphy BR, Chanock RM. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology. 2003 Sep 15;314(1):190-5.

Pugachev KV, Guirakhoo F, Trent DW, Monath TP. Traditional and novel approaches to flavivirus vaccines. Int J Parasitol. 2003 May;33(5-6):567-82. Review.

Responsible Party:	Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier:	NCT00094718 History of Changes
Other Study ID Numbers:	CIR 206, H.22.04.10.06.A1
Study First Received:	October 21, 2004
Last Updated:	January 18, 2008
Health Authority:	United States: Food and Drug Administration

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

Chimeric Virus Vaccine
West Nile Virus
Dengue Virus

Additional relevant MeSH terms:

Encephalitis
West Nile Fever
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Central Nervous System Infections
Encephalitis, Arbovirus
Arbovirus Infections
Encephalitis, Viral
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on February 12, 2012