Brief Title
New Study - Humoral Response to Tick-borne Encephalitis Vaccine in Elderly
Official Title
Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?
Brief Summary
The risk for tick borne encephalitis increases in Sweden. Together with an increased
awareness of the possibility to acquire protection by vaccination, this has led to an
increase in the number of doses of the vaccine distributed in Sweden each year - now being
approximately 400.000. The first year, two doses with an interval of 1 month is recommended
for the general population, followed by a third dose approximately one year later and an
additional booster dose three years after the third.
Preliminary results from a previous study showed a higher percentage protected (=titer at
least 10) after 3 doses than after 2 doses (Rombo et al. EUDRA CT 2011 001348-31, unpublished
information). In the same study, there were no differences between those who were vaccinated
0+7+21 compared to 0+30+90. The investigators were surprised to find marked differences
between 2 and 3 doses also in the younger control group.
The investigators therefore aim to confirm results in a new study and to add a group with a
double dose at day 0 and then a single dose at day 30 and 360
Detailed Description
The risk for tick borne encephalitis increases in Sweden. Together with an increased
awareness of the possibility to acquire protection by vaccination, this has led to an
increase in the number of doses of the vaccine distributed in Sweden each year - now being
approximately 400.000. The first year, two doses with an interval of 1 month is recommended
for the general population, followed by a third dose approximately one year later and an
additional booster dose three years after the third.
The manufacturer of Encepur recommended a total of three doses to this age group using the
same regimen as with "accelerated vaccination schedule (0+7+21 days). Unfortunately,
geometrical mean of titers after 3 doses with the accelerated schedule is not superior to 2
doses given at 0+30 days The manufacturer of FSME-immune instead recommended that serology
should be checked one month after the second dose and that a third dose should be given if
titers are not sufficient (0+30+60 days). Unfortunately, determinations of titers in a large
number of samples put severe strain on logistics and is not feasible in Sweden.
In order to try to improve immunity in the age group 60+ , the Department of Communicable
Disease Control and Prevention in Stockholm therefore recommends a third dose two months
after the first two doses to the age group 60+ (= 0+30+90 days).
Preliminary results from a previous study showed a higher percentage protected (=titer at
least 10) after 3 doses than after 2 doses (Rombo et al. EUDRA CT 2011 001348-31, unpublished
information). In the same study, there were no differences between those who were vaccinated
0+7+21 compared to 0+30+90. The investigators were surprised to find marked differences
between 2 and 3 doses also in the younger control group
Primary aim: To study whether any differences remain before and one month after an additional
dose at the following season Secondary aim: To study whether an additional dose of TBE
vaccine 2 months after the second dose will improve protection in an age group 50+.
Primary endpoint: Serum concentration of neutralising antibodies against tick borne
encephalitis one month after an additional dose the following year
Secondary endpoints: Serum concentration of neutralising antibodies against tick borne
encephalitis one month after two or three doses.
Calculation of power: Depend on whether the aim is to determine differences in geometric mean
titers or differences in seroconversion rate. The investigators prefer the former but have
not settled for the least difference which would be interesting.
Inclusion critera: Age 50 years or more. Exclusion critera: previous tick borne encephalitis
infection. Previously immunized with tick borne encephalitis vaccine. Anaphylactic reac tion
to egg protein. Any disease or therapy which might suppress the immune response. Vaccination
should be delayed if a participant has fever.
Study design. The investigators intend to give FSME-immune to 4 groups with varying
vaccination schedules (see below) 50 participants will be randomized to each Group. A younger
age group (50 participants between 18-49 years) will serve as controls and will be given
FSME-immune according to standard recommendations (0+30 days)
Days 0 7 21 30 90 360 Vaccine group 1 x x x Vaccine group 2 x x x x Vaccine group 3 x x x x
Vaccine group 4 xx x x Controls x x x
Blood samples (10 ml of blood) will be obtained for humoral response as shown below
Days 0 60 120 360 400 Group 1 x x x x x Group 2 x x x x x Group 3 x x x x x Group 4 x x x x x
Controls x x x x x
Analyses Samples are analysed for neutralising antibodies at the Swedish institute for
Infectious disease control - other options possible.
Study Phase
Phase 2/Phase 3
Study Type
Interventional
Primary Outcome
Serum concentration of neutralising antibodies against TBE one month after two or three doses.
Secondary Outcome
Serum concentration of neutralising antibodies against TBE one month after the dose which will be given a year later
Condition
Tick-borne Encephalitis
Intervention
FSME-immune
Study Arms / Comparison Groups
TBE vaccine at 0+30 days
Description: This group of 50 participants will follow the standard recommendation and will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 days during the first year and an additional dose one year later
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
250
Start Date
January 2015
Completion Date
June 2017
Primary Completion Date
February 2016
Eligibility Criteria
Inclusion Criteria:
- Age 50 years or more (Control group 18 years)
- generally healthy
- no immunosuppressive condition
- fertile women must use contraceptives
Exclusion Criteria:
- Previous TBE infection
- Previously immunized with TBE vaccine
- Anaphylactic reaction to egg protein
- Any disease or therapy which might suppress the immune response
- Vaccination should be delayed if a participant has fever
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
lars rombo, MD, ,
Location Countries
Finland
Location Countries
Finland
Administrative Informations
NCT ID
NCT02318069
Organization ID
2011/4-31/2 - B
Responsible Party
Principal Investigator
Study Sponsor
Sormland County Council, Sweden
Collaborators
Karolinska Institutet
Study Sponsor
lars rombo, MD, Principal Investigator, Karolinska Institutet
Verification Date
February 2021