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

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.

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/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.

Study Type

Interventional

Enrollment (Actual)

26

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
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Center for Immunization Research, Johns Hopkins School of Public Health (DC Location)
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Center for Immunization Research, Johns Hopkins School of Public Health (MD Location)

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

Yes

Genders Eligible for Study

All

Description

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

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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Time Frame: Throughout study
Throughout study
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
At study entry, Days 28 and 42 after first vaccination, and Days 180, 208, and 222 after second vaccination

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Throughout study
Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU)
Time Frame: Throughout study
Throughout study
Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts
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

Investigators

  • Principal Investigator: Anna Durbin, M.D., Center for Immunization Research (CIR), Johns Hopkins 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

Helpful Links

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

March 1, 2008

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

September 27, 2007

First Submitted That Met QC Criteria

September 27, 2007

First Posted (Estimate)

September 28, 2007

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 242
  • WIRB Protocol Number 20071891

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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