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

December 31, 2012 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of vaccine-related adverse effects, graded by severity, for each dose
Time Frame: Throughout study
Throughout study
Immunogenicity of vaccine against WN virus
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the durability of the antibody response
Time Frame: At Day 180
At Day 180
To assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time Frame: Throughout study
Throughout study
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
Time Frame: Throughout study
Throughout study
To assess the immunogenicity of the WN/DEN4-3'delta30 vaccine against WN wild-type virus
Time Frame: Throughout study
Throughout study
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
At study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

April 1, 2005

Study Completion (Actual)

April 1, 2005

Study Registration Dates

First Submitted

October 21, 2004

First Submitted That Met QC Criteria

October 21, 2004

First Posted (Estimate)

October 22, 2004

Study Record Updates

Last Update Posted (Estimate)

January 3, 2013

Last Update Submitted That Met QC Criteria

December 31, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR 206
  • H.22.04.10.06.A1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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