Safety of and Immune Response to a West Nile Virus Vaccine (WN/DEN4delta30) in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00537147
First received: September 27, 2007
Last updated: December 31, 2012
Last verified: December 2012
  Purpose

West Nile (WN) virus infection is an emerging disease. Infection with WN virus may lead to paralysis, coma, and death. The purpose of this study is to determine the safety of and immune response to a two-dose regimen of 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
Biological: WN/DEN4delta30 vaccine
Biological: Placebo
Phase 1

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 a 2-Dose Regimen of West Nile/Dengue 4-3'delta30 Chimeric Virus Vaccine (WN/DEN4delta30), a Live Attenuated Vaccine for West Nile Encephalitis

Resource links provided by NLM:


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 both intensity and severity through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Immunogenicity, determined by anti-WN/DEN4 neutralizing antibody titer [ Time Frame: At study entry, Days 28 and 42 after first vaccination, and Days 180, 208, and 222 after second vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the frequency, quantity, and duration of viremia after each dose of vaccine by dose cohort (10^4 or 10^5 PFU) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: March 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
1 vaccination of a 10^4 plaque-forming units (PFU) dose of WN/DEN4delta30 vaccine administered as 0.5 ml subcutaneously in deltoid at study entry and Day 180.
Biological: WN/DEN4delta30 vaccine
Live attenuated WN/DEN4delta30 vaccine (one of two doses)
Experimental: 2
1 vaccination of a 10^5 PFU dose of WN/DEN4delta30 vaccine administered as 0.5 ml subcutaneously in deltoid at study entry and Day 180.
Biological: WN/DEN4delta30 vaccine
Live attenuated WN/DEN4delta30 vaccine (one of two doses)
Placebo Comparator: 3
1 vaccination of a placebo administered as 0.5 ml subcutaneously in deltoid at study entry and Day 180.
Biological: Placebo
Placebo for WN/DEN4delta30 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/DEN4delta30, which is derived from the DEN4 dengue virus and wild-type WN serotypes.

This study will last at least 32 weeks. Participants in Cohort 1 will be randomly assigned to receive 1X10^4 plaque-forming units (PFU) WN/DEN4delta30 or placebo at study entry and Day 180. Cohort 2 will be randomly assigned to receive a higher dose of WN/DEN4delta30, 10^5 PFU, or placebo at study entry and Day 180. Immediately after receiving their injections, participants will be observed for 30 minutes for immediate adverse reactions.

After each vaccination, participants will be asked to monitor their temperatures three times every day for 16 days. Study visits will occur every other day after each vaccination until Day 16, followed by three additional visits at selected days through Day 180 post-vaccination. Blood collection, medical history, vital signs measurement, and a targeted physical exam will occur at all visits. Participants will also be required to keep temperature diaries until Day 16 after vaccination. Female participants will have a urine pregnancy test performed within 60 days of study entry, and on Days 28, 42, 150, 180, 208, and 222. Pregnancy prevention counseling will occur 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:

  • Good general health
  • Available for the duration of the trial
  • Willing to use acceptable forms of contraception for the duration of the study

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, affects the ability of the volunteer to understand and cooperate with the study
  • Neutropenia (abnormally low neutrophil count)
  • Alcohol or drug abuse within 12 months prior to study entry
  • Elevated levels of alanine aminotransferase (ALT) and serum creatinine
  • History of severe allergic reaction or anaphylaxis
  • Severe asthma
  • 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
  • Surgical removal of spleen
  • Blood products within 6 months prior to study entry
  • History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
  • Previously received a licensed or experimental yellow fever or dengue vaccine
  • Investigational agent within 30 days of study entry
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537147

Locations
United States, District of Columbia
Center for Immunization Research, Johns Hopkins School of Public Health (DC Location)
Washington, District of Columbia, United States, 20037
United States, Maryland
Center for Immunization Research, Johns Hopkins School of Public Health (MD Location)
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
Investigators
Principal Investigator: Anna Durbin, M.D. Center for Immunization Research (CIR), Johns Hopkins School of Public Health
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00537147     History of Changes
Other Study ID Numbers: CIR 242, WIRB Protocol Number 20071891
Study First Received: September 27, 2007
Last Updated: December 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Chimeric West Nile Virus
West Nile Virus
Dengue Virus

Additional relevant MeSH terms:
West Nile Fever
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on July 20, 2014