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

West Nile Fever Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00537147
• Other study ID #: CIR 242
• Secondary ID: WIRB Protocol Nu
• Status: Completed
• Phase: Phase 1
• First received: September 27, 2007
• Last updated: December 31, 2012
• Start date: March 2008
• Est. completion date: June 2009

Study information

• Verified date: December 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• West Nile Fever

Intervention

Biological:
• WN/DEN4delta30 vaccine
Live attenuated WN/DEN4delta30 vaccine (one of two doses)
• Placebo
Placebo for WN/DEN4delta30 vaccine

Locations

Country	Name	City	State
United States	Center for Immunization Research, Johns Hopkins School of Public Health (MD Location)	Baltimore	Maryland
United States	Center for Immunization Research, Johns Hopkins School of Public Health (DC Location)	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Johns Hopkins Bloomberg School of Public Health

Country where clinical trial is conducted

United States, 

References & Publications (2)

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance		Throughout study	Yes
Primary	Immunogenicity, determined by anti-WN/DEN4 neutralizing antibody titer		At study entry, Days 28 and 42 after first vaccination, and Days 180, 208, and 222 after second vaccination	No
Secondary	Assess the frequency, quantity, and duration of viremia after each dose of vaccine by dose cohort (10^4 or 10^5 PFU)		Throughout study	No
Secondary	Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU)		Throughout study	No
Secondary	Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts		At study completion	No

External Links

•   Click here for the Johns Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR) Web site