Tick-borne EncephalitisPhase 2/3NCT01361776
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 6 sites in 2 countries.
Trial summary
Antibody titers after tick-borne encephalitis (TBE) vaccination are less in elderly and vaccination breakthroughs are more common in this age group. This has prompted Swedish authorities to recommend an additional dose in the initial vaccination schedule (= 0+30+90 days instead of the usually recommended 0+30 days. 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
- 200 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Sep 2011to Jun 2014
- 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
- 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
6 sites in 2 countries.
6 sites in 2 countries
Sweden5 sites
Dept infectious diseases
Eskilstuna, 631 88
Dept infectious diseases
Karlstad, 651 85
Department of infectious diseases
Örebro
Department of infectious diseases
Stockholm, 17176
Dept infectious diseases
Uppsala, 751 85
About this study
Official title: Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?
Antibody titers after tick-borne encephalitis (TBE) vaccination are less in elderly and vaccination breakthroughs are more common in this age group. This has prompted Swedish authorities to recommend an additional dose in the initial vaccination schedule (= 0+30+90 days instead of the usually recommended 0+30 days. The investigators intend to evaluate this regime.
Read the detailed description
The risk for TBE 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.
Recent studies show that the antibody titers against TBE are substantially less in an older population. This is in line with the present recommendation from Austria that booster intervals should be shortened to 3 years in the age group 60+. It is also in line with a report of vaccination failures where 13/27 patients were older than 60 years According to a study by Jilkowa et al, 18 % (38/185) in the age group 60+ did not achieve putative levels of antibody titers after the first two doses. Therefore, the manufacturer of Encepur recommends a total of three doses to this age group using the same regimen as with "accelerated vaccination schedule (0+7+21 days). Unfortunately, GMT (geometrical mean of titers) after 3 doses with the accelerated schedule are not superior to 2 doses given at 0+30 days.
The manufacturer of FSME-immun instead recommends 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+60 days).
Study design. The investigators intend to give FSME-immune to 3 groups with varying vaccination schedules ( 0+7+21, 0+30 or 0+30+90. 50 participants will be randomized to each group. Half of them will be between 50-59 years and half will be at least 60 years old. 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).
Serum samples (10 ml of blood) will be obtained at five times: 0,60,120,360 and 400 days after first dose Samples will be 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 4 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 vaccinte 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 |
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 posted27 May 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2013
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sormland County Council, Sweden
- Sponsor type
- University, hospital or other
- 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
- NCT01361776
- Sponsor's protocol ID
- 2011/4-31/2
- Status last verified
- Nov 2015
- First submitted
- 25 May 2011
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kantele A, Rombo L, Vene S, Kundi M, Lindquist L, Erra EO. Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial. Vaccine. 2022 Feb 23;40(9):1299-1305. doi: 10.1016/j.vaccine.2022.01.022. Epub 2022 Jan 31.
PubMed 35101266
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. 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
- NCT01361776
- Acronym / sponsor ID
- 2011/4-31/2
- Conditions
- Tick-borne Encephalitis
- Keywords
- immune response, TBE-vaccine, elderly, additional doses
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Sormland County Council, SwedenUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 27 May 2011 (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.
Antibody titers after tick-borne encephalitis (TBE) vaccination are less in elderly and vaccination breakthroughs are more common in this age group. This has prompted Swedish authorities to recommend an additional dose in the initial vaccination schedule (= 0+30+90 days instead of the usually recommended 0+30 days. The investigators intend to evaluate this regime.
Detailed description
The risk for TBE 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.
Recent studies show that the antibody titers against TBE are substantially less in an older population. This is in line with the present recommendation from Austria that booster intervals should be shortened to 3 years in the age group 60+. It is also in line with a report of vaccination failures where 13/27 patients were older than 60 years According to a study by Jilkowa et al, 18 % (38/185) in the age group 60+ did not achieve putative levels of antibody titers after the first two doses. Therefore, the manufacturer of Encepur recommends a total of three doses to this age group using the same regimen as with "accelerated vaccination schedule (0+7+21 days). Unfortunately, GMT (geometrical mean of titers) after 3 doses with the accelerated schedule are not superior to 2 doses given at 0+30 days.
The manufacturer of FSME-immun instead recommends 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+60 days).
Study design. The investigators intend to give FSME-immune to 3 groups with varying vaccination schedules ( 0+7+21, 0+30 or 0+30+90. 50 participants will be randomized to each group. Half of them will be between 50-59 years and half will be at least 60 years old. 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).
Serum samples (10 ml of blood) will be obtained at five times: 0,60,120,360 and 400 days after first dose Samples will be 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
- 4
| 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 vaccinte 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 |
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
- 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 4 arms | Biological | TBE vaccine at 0+30 days, TBE vaccine at 0+7+21 days, TBE vaccinte at 0+30+90 days, 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 18 Nov 2015.
- Derived from this study: PubMed 35101266Kantele A, Rombo L, Vene S, Kundi M, Lindquist L, Erra EO. Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial. Vaccine. 2022 Feb 23;40(9):1299-1305. doi: 10.1016/j.vaccine.2022.01.022. Epub 2022 Jan 31.
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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
6 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 6 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 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Sweden, Finland. 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?
On the ClinicalTrials.gov record for NCT01361776, which also lists 1 linked publication.
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 18 Nov 2015.