Tick-borne EncephalitisPhase 2/3NCT02318069
New Study - Humoral Response to Tick-borne Encephalitis Vaccine in Elderly
A Phase 2/3 study testing FSME-immune in people with Tick-borne Encephalitis, run by Sormland County Council, Sweden at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tick-borne Encephalitis
- What is being tested?
- FSME-immune
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2015to Jun 2017
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 50 years or more (Control group 18 years)
- generally healthy
- no immunosuppressive condition
- fertile women must use contraceptives
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?
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
Read the 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.
- Conditions
- Tick-borne Encephalitis
- Being tested
- FSME-immune
- Keywords
- immune response, TBE-vaccine, elderly, additional doses
- Medical subject headings
- Encephalitis, Tick-Borne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FSME-immuneBiological
0.5 ml im as scheduled in the 5 arms
| Study group | Role | What they receive |
|---|---|---|
| TBE vaccine at 0+30 days | Active comparator | 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 Receives: Biological: FSME-immune |
| TBE vaccine at 0+7+21 days | Active comparator | This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 7 +21 days during the first year and an additional dose one year later Receives: Biological: FSME-immune |
| TBE vaccine at 0+30+90 days | Active comparator | This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 + 90 days during the first year and an additional dose one year later Receives: Biological: FSME-immune |
| younger participants | Active comparator | This group of 50 participants in the age group 18-49 years 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 Receives: Biological: FSME-immune |
| double dose of vaccine | Active comparator | This group of 50 participants will be given two doses of TBE vaccine 0.5 ml FSME immune at the first day of the study and an additional dose at day 30 as well as one year later Receives: Biological: FSME-immune |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum concentration of neutralising antibodies against TBE one month after two or three doses.
Determination of neutralising antibodies one month after completion of the first years vaccination series
Measured: 18 months after the first dose
Secondary outcomes (1)
Serum concentration of neutralising antibodies against TBE one month after the dose which will be given a year later
Determination of neutralising antibodies one month after the dose which will be given a year later
Measured: 18 months after the first dose has been given
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionFeb 2016
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tick-borne EncephalitisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sormland County Council, Sweden
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet, Helsingfors university
- Responsible party
- Principal investigator, Lars Rombo, Sormland County Council, Sweden
- Investigators
- lars rombo, MD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02318069
- Sponsor's protocol ID
- 2011/4-31/2 - B
- Status last verified
- Feb 2021
- First submitted
- 12 Dec 2014
- Last updated
- 10 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?
- ClinicalTrials.gov ID
- NCT02318069
- Acronym / sponsor ID
- 2011/4-31/2 - B
- Conditions
- Tick-borne Encephalitis
- Keywords
- immune response, TBE-vaccine, elderly, additional doses
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Sormland County Council, SwedenUniversity, hospital or other
- Collaborators
- Karolinska Institutet, Helsingfors university
- Study start
- Jan 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 17 Dec 2014 (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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| TBE vaccine at 0+30 days | Active comparator | Biological: FSME-immuneThis 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 |
| TBE vaccine at 0+7+21 days | Active comparator | Biological: FSME-immuneThis group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 7 +21 days during the first year and an additional dose one year later |
| TBE vaccine at 0+30+90 days | Active comparator | Biological: FSME-immuneThis group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 + 90 days during the first year and an additional dose one year later |
| younger participants | Active comparator | Biological: FSME-immuneThis group of 50 participants in the age group 18-49 years 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 |
| double dose of vaccine | Active comparator | Biological: FSME-immuneThis group of 50 participants will be given two doses of TBE vaccine 0.5 ml FSME immune at the first day of the study and an additional dose at day 30 as well as one year later |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 50 years or more (Control group 18 years)
- generally healthy
- no immunosuppressive condition
- fertile women must use contraceptives
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| FSME-immune0.5 ml im as scheduled in the 5 arms | Biological | TBE vaccine at 0+30 days, TBE vaccine at 0+30+90 days, TBE vaccine at 0+7+21 days, double dose of vaccine, younger participants |
Primary outcome
Serum concentration of neutralising antibodies against TBE one month after two or three doses.
Time frame: 18 months after the first dose
Determination of neutralising antibodies one month after completion of the first years vaccination series
1 secondary outcome
Serum concentration of neutralising antibodies against TBE one month after the dose which will be given a year later
Time frame: 18 months after the first dose has been given
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 10 Feb 2021.
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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.
lars rombo, MD principal investigator
Karolinska Institutet
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing FSME-immune in people with Tick-borne Encephalitis, run by Sormland County Council, Sweden at 2 sites in 2 countries.
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 4 inclusion and 5 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 10 Feb 2021. 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 Finland, Sweden. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Serum concentration of neutralising antibodies against TBE one month after two or three doses. (time frame: 18 months after the first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2021.