A Phase II, Open Label Trial of a Vaccine (FSME-IMMUN 0.5 mL) Against Tick-borne Encephalitis (TBE) for NIAID Workers Manipulating Tick Borne Encephalitis Virus (TBEV) in the Laboratory
- Infection by tick-borne encephalitis virus (TBEV) is a significant health concern for humans in Europe and Asia. A vaccine is available in these regions and in Canada, but not in the United States. Research studies in Europe have shown the vaccine to be effective in preventing infection among the general population, where disease is transmitted either by the bite of an infected tick (most common) or by ingestion of contaminated unpasteurized milk or milk products. Persons who work with the virus in a research setting, however, have the potential of being exposed in unnatural ways, and may come into contact with concentrations of virus higher than those found naturally in ticks.
- The Food and Drug Administration is investigating the effectiveness of the existing vaccine. It is a killed vaccine, which means that it has been treated to ensure that it does not contain live agents (bacteria or virus). The manufacturer has tested the product for other possible contaminating agents and none have been detected. However, there is an unknown but small risk of exposure to undetected contaminating agents in the vaccine.
- To test the safety and immune response to a vaccine against tick-borne encephalitis virus (TBEV).
- To add a level of protection to persons who may have occupational exposure to TBEV to reduce their chances of developing infection from that exposure.
- Individuals 18 years of age or older who are in generally good health and have the potential for occupational exposure to TBEV at one of the two National Institute of Allergy and Infectious Diseases campuses.
- Subjects receiving the full series of the vaccine will receive at least three doses by injection in the upper arm. The first and third dose of study vaccine will be given in the muscle of the nondominant arm. The second dose will be given in the dominant arm.
- Participation will include at least 12 scheduled visits to the study center over approximately 3.5 years.
- An initial visit will take place 7 to 21 days prior to the first injection. Blood samples will be taken to test liver and kidney function, baseline antibody levels, and for possible pregnancy in female participants.
- Doses will be given on days 0, 14, and 161. Participants will be asked to complete a diary card on each day for one week following the vaccination to assess any reactions or side effects. At each visit after receipt of a vaccine, participants will be asked about any side effects.
- Blood will be drawn 14 days after the second injection and 21 days after the third injection in order to measure the level of antibodies and overall response to the vaccine.
- Subjects who develop a sufficiently high level of antibodies may (at the discretion of the laboratory chief) be allowed to work with strains of TBEV at Biosafety Level (BSL) 3 rather than BSL-4. Blood will be drawn annually for 3 years to determine antibody level and response to the vaccine. Booster doses will be provided if required.
Glycoprotein E, Flavivirus
NSI Protein, Flavivirus
Biological: FSME-IMMUN 0.5ml Baxter
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase II, Open Label Trial of a Vaccine (FSME-IMMUN 0.5 mL) Against Tick-Borne Encephalitis (TBE) for NIAID Workers Manipulating Tick-Borne Encephalitis Virus (TBEV) in the Laboratory|
- Determine the rate of development of both a level of anti-tick borne encephalitis antibody and viral neutralization titer that have been found to protect against TBEV infection after 3 doses of IM FSME-Immun. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Study Completion Date:||December 2016|
|Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Biological: FSME-IMMUN 0.5ml Baxter
This is an open label trial of a non-US licensed vaccine for tick-borne encephalitis. The vaccine has been licensed by Baxter, now following an acquisition by Pfizer Inc in Vienna, Austria since 2001, and has an extensive safety record in multiple European countries. Field effectiveness studies suggest > 99 percent protection against disease transmitted by the natural routes of either tick bite or ingestion of contaminated, unpasteurized milk. The vaccine is also considered to be effective against laboratory exposures and is used routinely for this purpose in European laboratories. The US Centers for Disease Control and Prevention and the National Institutes of Health acknowledge the effectiveness of the vaccine by allowing those who have received it to study tick-borne encephalitis virus (TBEV) in isolation facilities rated at BSL-3 rather than the more stringent BSL-4, with the exception of the Russian Spring-Summer Encephalitis strain.
Subjects will be personnel from 2 intramural campuses of the National Institute of Allergy and Infectious Diseases who may be exposed accidentally to any strain or serotype of viable TBEV. Approximately 160 individuals are eligible to participate. Inclusion and exclusion criteria are defined. The rapid immunization schedule (injections on Days 0, 14, and 161) will be used and subjects will have labs drawn 21 days after the 2nd, 3rd and 4th vaccine injections to determine seroconversion. Subjects who seroconvert to TBEV will be offered a booster dose of the vaccine 3 years from the date of receipt of the third dose of the vaccine. Subjects who are seropositive at entry into the study will be offered a booster dose of the vaccine every 3 years from Day 0.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01031537
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Montana|
|Rocky Mountain Laboratory (RML)|
|Hamilton, Montana, United States, 59840|
|Principal Investigator:||James M Schmitt, M.D.||National Institutes of Health Clinical Center (CC)|