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

Primary Purpose

West Nile Fever

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

WN/DEN4delta30 vaccine

Placebo

About this trial

This is an interventional prevention trial for West Nile Fever focused on measuring Chimeric West Nile Virus, West Nile Virus, Dengue Virus

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Center for Immunization Research, Johns Hopkins School of Public Health (DC Location)
Center for Immunization Research, Johns Hopkins School of Public Health (MD Location)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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.

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.

1 vaccination of a placebo administered as 0.5 ml subcutaneously in deltoid at study entry and Day 180.

Outcomes

Primary Outcome Measures

Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance

Immunogenicity, determined by anti-WN/DEN4 neutralizing antibody titer

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)

Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU)

Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts

Full Information

NCT ID

NCT00537147

First Posted

September 27, 2007

Last Updated

December 31, 2012

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

1. Study Identification

Unique Protocol Identification Number

NCT00537147

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

West Nile Fever

Keywords

Chimeric West Nile Virus, West Nile Virus, Dengue Virus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm Type

Placebo Comparator

Arm Description

1 vaccination of a placebo administered as 0.5 ml subcutaneously in deltoid at study entry and Day 180.

Intervention Type

Biological

Intervention Name(s)

WN/DEN4delta30 vaccine

Intervention Description

Live attenuated WN/DEN4delta30 vaccine (one of two doses)

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Placebo for WN/DEN4delta30 vaccine

Primary Outcome Measure Information:

Title

Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance

Time Frame

Throughout study

Title

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

Secondary Outcome Measure Information:

Title

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

Title

Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU)

Time Frame

Throughout study

Title

Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts

Time Frame

At study completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anna Durbin, M.D.

Organizational Affiliation

Center for Immunization Research (CIR), Johns Hopkins School of Public Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Center for Immunization Research, Johns Hopkins School of Public Health (DC Location)

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20037

Country

United States

Facility Name

Center for Immunization Research, Johns Hopkins School of Public Health (MD Location)

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15056045

Citation

Chang GJ, Kuno G, Purdy DE, Davis BS. Recent advancement in flavivirus vaccine development. Expert Rev Vaccines. 2004 Apr;3(2):199-220. doi: 10.1586/14760584.3.2.199.

Results Reference

background

PubMed Identifier

14517072

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. doi: 10.1016/s0042-6822(03)00450-1.

Results Reference

background

Links:

URL

http://www.jhsph.edu/cir

Description

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

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

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