West Nile Fever EncephalitisPhase 1NCT00094718
Safety of and Immune Response to a West Nile Virus Vaccine (WN/DEN4-3'delta30) in Healthy Adults
A Phase 1 study testing WN/DEN4-3'delta30 in people with West Nile Fever Encephalitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- West Nile Fever Encephalitis
- What is being tested?
- WN/DEN4-3'delta30
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2005to Apr 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing to be followed for the duration of the study
- Willing to use acceptable methods of contraception
- Good general health
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins School of Public Health
Baltimore, Maryland, 21205
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
About this study
Official title: 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.
Read the 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.
- Conditions
- West Nile Fever Encephalitis
- Being tested
- WN/DEN4-3'delta30, Placebo
- Keywords
- Chimeric Virus Vaccine, West Nile Virus, Dengue Virus
- Medical subject headings
- West Nile Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WN/DEN4-3'delta30Biological
Live attenuated WN/DEN4-3'delta30 vaccine (one of three doses)
PlaceboBiological
Placebo for WN/DEN4-3'delta30 vaccine
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | One subcutaneous vaccination with WN/DEN4-3'delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm. Receives: Biological: WN/DEN4-3'delta30 |
| 2 | Experimental | 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. Receives: Biological: WN/DEN4-3'delta30 |
| 3 | Experimental | 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. Receives: Biological: WN/DEN4-3'delta30 |
| 4 | Placebo comparator | One subcutaneous vaccination with placebo vaccine into the deltoid region of either arm. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of vaccine-related adverse effects, graded by severity, for each dose
Measured: Throughout study
Immunogenicity of vaccine against WN virus
Measured: Throughout study
Secondary outcomes (5)
To assess the durability of the antibody response
Measured: At Day 180
To assess the frequency, quantity, and duration of viremia in each dose cohort studied
Measured: Throughout study
To assess the immunogenicity of the WN/DEN4-3'delta30 vaccine against WN wild-type virus
Measured: 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
Measured: At study completion
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2004 (estimated)
- Study startFeb 2005
- Primary completionApr 2005
- Study completionApr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for West Nile Fever EncephalitisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Responsible party
- Sponsor
- Investigators
- Anna Durbin, MD, Principal investigator, Center for Immunization Research, Johns Hopkins School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094718
- Sponsor's protocol ID
- CIR 206
- Other IDs
- H.22.04.10.06.A1
- Status last verified
- Dec 2012
- First submitted
- 21 Oct 2004
- Last updated
- 3 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15056045Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. doi: 10.1016/s0065-3527(03)61013-4.
PubMed 14714441Monath TP, McCarthy K, Bedford P, Johnson CT, Nichols R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F. Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections. Vaccine. 2002 Jan 15;20(7-8):1004-18. doi: 10.1016/s0264-410x(01)00457-1.
PubMed 11803060Pletnev 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.
PubMed 14517072Pugachev KV, Guirakhoo F, Trent DW, Monath TP. Traditional and novel approaches to flavivirus vaccines. Int J Parasitol. 2003 May;33(5-6):567-82. doi: 10.1016/s0020-7519(03)00063-8.
PubMed 12782056
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00094718
- Acronym / sponsor ID
- CIR 206
- Conditions
- West Nile Fever Encephalitis
- Keywords
- Chimeric Virus Vaccine, West Nile Virus, Dengue Virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Study start
- Feb 2005
- Primary completion
- Apr 2005 (actual)
- Study completion
- Apr 2005 (actual)
- First posted
- 22 Oct 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: WN/DEN4-3'delta30One subcutaneous vaccination with WN/DEN4-3'delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm. |
| 2 | Experimental | Biological: WN/DEN4-3'delta30One 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. |
| 3 | Experimental | Biological: WN/DEN4-3'delta30One 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. |
| 4 | Placebo comparator | Biological: PlaceboOne subcutaneous vaccination with placebo vaccine into the deltoid region of either arm. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Willing to be followed for the duration of the study
- Willing to use acceptable methods of contraception
- Good general health
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WN/DEN4-3'delta30Live attenuated WN/DEN4-3'delta30 vaccine (one of three doses) | Biological | 1, 2, 3 |
| PlaceboPlacebo for WN/DEN4-3'delta30 vaccine | Biological | 4 |
Primary outcome
Frequency of vaccine-related adverse effects, graded by severity, for each dose
Time frame: Throughout study
Immunogenicity of vaccine against WN virus
Time frame: Throughout study
5 secondary outcomes
To assess the durability of the antibody response
Time frame: At Day 180
To assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time frame: Throughout study
To assess the immunogenicity of the WN/DEN4-3'delta30 vaccine against WN wild-type virus
Time frame: 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
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2013.
- Background: PubMed 15056045Chang 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.
- Background: PubMed 14714441Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. doi: 10.1016/s0065-3527(03)61013-4.
- Background: PubMed 11803060Monath TP, McCarthy K, Bedford P, Johnson CT, Nichols R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F. Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections. Vaccine. 2002 Jan 15;20(7-8):1004-18. doi: 10.1016/s0264-410x(01)00457-1.
- Background: PubMed 14517072Pletnev 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.
- Background: PubMed 12782056Pugachev KV, Guirakhoo F, Trent DW, Monath TP. Traditional and novel approaches to flavivirus vaccines. Int J Parasitol. 2003 May;33(5-6):567-82. doi: 10.1016/s0020-7519(03)00063-8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Durbin, MD principal investigator
Center for Immunization Research, Johns Hopkins School of Public Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing WN/DEN4-3'delta30 in people with West Nile Fever Encephalitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of vaccine-related adverse effects, graded by severity, for each dose (time frame: Throughout study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094718, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2013.