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



Status:Terminated
Conditions:Infectious Disease
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - 100
Updated:10/8/2017
Start Date:September 25, 2009
End Date:December 23, 2016

Use our guide to learn which trials are right for you!

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

Background:

- 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.

Objectives:

- 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.

Eligibility:

- 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.

Design:

- 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.

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.

- INCLUSION CRITERIA:

All subjects must meet the following criteria at study entry:

- Be engaged in activities that place them at potential risk of occupational exposure to
TBEV in its viable form at one of the participating intramural laboratories of NIAID

- Be 18 years of age or older at the time of the first immunization.

- Comprehend the study requirements.

- Provide written informed consent to participate in this study.

- Be in good health as determined by the Investigator, based upon medical history and a
targeted physical examination.

- Have a stable health status as determined by the Investigator.

- Have access to a consistent means of telephone contact, which may be either in the
home or at the workplace, land line or mobile, but NOT a pay phone or other
multiple-user device (i.e., a common use phone serving multiple rooms or apartments).

- Express availability for the required study period, and ability to attend scheduled
visits.

EXCLUSION CRITERIA:

The following criteria should be checked at the time of the study entry. If any apply, the
subject will not be included in the study:

- The subject must not be participating in any other trial of an investigational drug or
vaccine for 1 month prior to the first injection through until 21 days after the third
injection. (Given the nature of the work these study subjects engage in, exemptions to
this proscription may be granted on a case by case basis after discussion between the
Investigator and the IRB.)

- The presence on the day of immunization of an oral temperature of >101.2 degrees F or
acute symptoms other than mild severity.

- Active systemic infectious process as determined by review of systems and physical
examination. The subject may be enrolled at a later date once the illness has
resolved.

- Known immune suppression, such as that associated with human immunodeficiency virus
infection, or other condition, to the extent that, in the opinion of the Investigator,
the subject is likely to have a poor response to the vaccine. This information will be
obtained by history only. Serologic screening for these diseases will not be
performed.

- Presence of evidence of substance abuse or of neurological or psychiatric diagnoses
which, even if clinically stable, are deemed by the Investigator to render the
potential subject unable/unlikely to report promptly any adverse reactions to the
vaccine.

- Current diagnosis of leukemia, Hodgkin s disease, non-Hodgkin s lymphoma, or any other
cancer, autoimmune disease such as lupus, which is in and of itself a cause of
immunosuppression to the point that, in the opinion of the Investigator, the subject
is likely to have a poor response to the vaccine.

- Currently receiving systemic immunosuppressive chemotherapy or immunotherapy
(including glucocorticoids) resulting in immune suppression to the point that, in the
opinion of the Investigator, the subject is likely to have a poor response to the
vaccine.

- Any neurological condition in which (in the opinion of the Investigator) the integrity
of the blood brain barrier may have been compromised.

- Licensed vaccines are not exclusionary but should be given at least 14 days before or
after immunization (applies to each of the 3 scheduled TBEV injections) for
inactivated vaccines and 30 days before or after immunization with any live vaccines.
This is in order to avoid potential confusion of adverse reactions. (Given the nature
of the work these study subjects engage in, exemptions to this proscription may be
granted on a case-by-case basis after discussion between the Investigator and the
IRB.).

- Previous anaphylactic reaction to any TBE vaccine.

Known or suspected anaphylactic reaction to any constituent of FSME IMMUN, to include
formaldehyde, protamine sulfate, gentamicin and neomycin, or current egg allergy.

- Known pregnancy, or anticipating becoming pregnant in the first 8 months of the study
or a positive urine beta-human chorionic gonadotropin (beta hCG) test result prior to
immunization. If subjects become pregnant at some point in time after the 1st
injection, no further injections will be given until after the pregnancy is completed,
they are no longer nursing or have a negative beta-hCG result.

- Lactating or nursing.

- Women of child bearing potential (defined as pre-menopausal who have not undergone
either hysterectomy or tubal ligation) who lack a history of reliable contraceptive
practices. Reliable contraceptive practices (for the first 8 months of the study and
within 21 days prior to or 42 days after booster immunizations) include:

- Consistent abstinence from heterosexual activity

- Consistent use of combined or progestogen oral contraceptives

- Injectable progestogen

- Implants of levonorgestrel

- Estrogen or estrogen/progestogen vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS)

- Successful vasectomy of the sole male partner, or

- Double barrier method (condom or occlusive cap plus spermicidal agent)

- A history of a prior infection with TBEV or previously receiving a TBE vaccine will
not be considered as an exclusionary criterion for immunization through this protocol.
However, these subjects antibody titer data will not be included in the statistical
analysis.

- Any other conditions, which in the Investigator s judgment, might result in an
increased risk to the subject, or would affect their participation in the study.
Additionally the Investigator has the ability to exclude a subject if for any reason
he/she feels the subject is not a good candidate for the study or will not be able to
follow study procedures.
We found this trial at
2
sites
Hamilton, Montana 59840
?
mi
from
Hamilton, MT
Click here to add this to my saved trials
9000 Rockville Pike
Bethesda, Maryland 20892
Phone: 800-411-1222
?
mi
from
Bethesda, MD
Click here to add this to my saved trials