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Tick Borne EncephalitisPhase 2NCT01991067

Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

A Phase 2 study testing TBE virus vaccine in people with Tick Borne Encephalitis, run by Medical University of Vienna at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients undergoing allogeneic blood and marrow transplantation (HSCT) experience a prolonged period of dysfunctional immunity. Systematic reimmunization is necessary at appropriate time intervals following transplantation to re-establish immunity. Vaccination practices after HSCT remain varied and data sparse. 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?
TBE virus vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteAustria
Study dates
Jul 2014to 28 Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Male and female subjects will be eligible for participation in this study if they:
  • Are ≥18 years on the day of screening
  • Had undergone an allogeneic HSCT 11 to 13 months ago (study population)
  • Are clinical healthy without previous TBE vaccination (control group)
  • Have an understanding of the study, agree to its provisions, and give written informed consent prior to study entry
  • If female and capable of bearing children - have a negative urine pregnancy test result at study entry and agree to employ adequate birth control measures for the duration of the study

Who cannot join

  • Subjects will be excluded from participation in this study if they:
  • Have received a TBE vaccination following HSCT
  • Suffer from extremely severe acute graft-versus host disease and therefore receive prednisone >0.5 mg/kg bodyweight as part of a combination therapy or a three agent immunosuppressive treatment (because in these HSCT patients any type of vaccination has to be postponed until immunosuppression is reduced to a double combination or prednisone <0.5 mg/kg bodyweight)
  • Suffer from or have a history of previous TBE virus infection or vaccination, previous dengue virus infection or vaccination against yellow fever or Japanese encephalitis
  • Have any acute febrile illness in the 2 weeks prior to or at the time of enrolment
  • Have a history of severe allergic reactions or anaphylaxis after vaccination
  • If female, are pregnant or lactating.
  • If belonging to the healthy control group, are immunosuppressed (suffer from or have a history of immune mediated diseases, long-term use of corticosteroids, hemodialysis, chronic renal insufficiency, liver cirrhosis Child-Pugh class C, hematooncological malignant disease, solid organ transplant, HSCT)

Trial locations and contacts

1 site in 1 country.

Austria1 site

  • Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine

    Vienna, 1090

Other trials in Austria

About this study

Official title: Characterization of Humoral and Cellular Immunity for Tick-borne Encephalitis (TBE) Vaccination in Allogeneic Blood and Marrow Graft Recipients: a Pilot Study

Patients undergoing allogeneic blood and marrow transplantation (HSCT) experience a prolonged period of dysfunctional immunity. Systematic reimmunization is necessary at appropriate time intervals following transplantation to re-establish immunity. Vaccination practices after HSCT remain varied and data sparse. Tick-borne encephalitis (TBE) is one of the most severe infections of the central nervous system caused by a tick-borne flavivirus. There is no specific treatment, and prevention with the vaccine is the only intervention available. To assess the efficacy of TBE vaccination in adult allogeneic HSCT recipients compared to an age-matched and sex-matched control group of healthy volunteers without previous TBE vaccination, a prospective open-label phase II pilot study on humoral and cellular immune responses after use of TBE vaccine (FSME Immun) will be performed. As primary end point the outcome of the neutralization test (NT) against TBE will be assessed in a total of 26 HSCT patients one year after HSCT and in 26 healthy volunteers, namely four weeks after the second vaccination. Therefore, the number of subjects with NT titres against TBE virus >10, assumed to be the threshold for antibody-mediated protection will be evaluated. As secondary endpoints, antibody concentrations of TBE enzyme-linked immunosorbent assay before and four weeks after the second and third vaccination and antibody concentrations of NT against TBE four weeks after primary immunization. To evaluate cellular immune responses, lymphocyte proliferations assays and cytokine detection assays will be performed. In a subgroup analysis, these secondary endpoints will be compared between healthy volunteers, HSCT patients without immunosuppressive treatment and HSCT patients receiving immunosuppressive agents. Additionally, immune reconstitution by analysis of peripheral blood lymphocyte subsets and serum immunoglobulin levels will be evaluated prior to vaccination, after twelve weeks and prior to the third vaccination in HSCT patients only.

Being tested
TBE virus vaccine
Keywords
Marrow transplant recipients
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.

  • TBE virus vaccineBiological

    Also called FSME Immun

    TBE virus vaccine FSME Immun is used in both arms for the study population and the control group

Study groups in NCT01991067
Study groupRoleWhat they receive
HSCT patients / TBE virus vaccineActive comparatorStudy population: patients who had undergone an allogeneic HSCT 11 to 13 months ago Eligible patients will receive at least two TBE vaccinations (study visit 1 - day 0, study visit 2 -1month after the first vaccination) with a total of two doses of the TBE vaccine FSME-IMMUN®. Whenever possible, the patients will receive complete primary vaccination with a third dose of TBE vaccine (study visit 9 - 9 to 12 months after the first vaccination).
Receives: Biological: TBE virus vaccine
healthy volunteers / TBE virus vaccineActive comparatorClinical healthy volunteers will receive at least two TBE vaccinations (study visit 1 - day 0, study visit 2 -1month after the first vaccination) with a total of two doses of the TBE vaccine FSME IMMUN®. Whenever possible, the volunteers will receive complete primary vaccination with a third dose of TBE vaccine FSME IMMUN® (study visit 9 - 12 months after the first vaccination).
Receives: Biological: TBE virus vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Outcome of the Neutralization Test (Number of Subjects With Antibody Response Measured by Neutralization Assay)

    The Primary endpoint of this study was the antibody Response after TBE-vaccination as measured by neutralization assay four weeks after second vaccination. Antibody response was defined as a Composite endpoint by a NT-titer of >=10, and at least a two-fold increase from baseline (or titer above the highest level of measurement

    Measured: four weeks after the second vaccination

Secondary outcomes (8)

  1. Antibody Response as Measured by TBE-ELISA After Second Vaccination

    The antibody response after TBE-vaccination four weeks after second vaccination was measured by ELISA defined by a ELISA titer of >=220 Vienna Units and at least a two-fold increase of titer from baseline

    Measured: comparison between baseline and four weeks after second vaccination

  2. Change of Antibody Concentration of NT Titer

    Geometric mean fold change of NT titer between baseline and four weeks after third vaccination was compared between HSCT patients and healthy controls

    Measured: between baseline and four weeks after the third vaccination

  3. Lymphocyte Proliferation as a Measure of Cellular Immune Response in the Study Population Versus the Control Group Prior Vaccination

    Baseline data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE Antigen. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

    Measured: before vaccination

  4. Fold Induction in IL13 Cytokine Levels Before Vaccination (Baseline) in the Study Population Versus the Control Group

    Determination of secreted IL13 cytokine levels iwas performed using the Luminex System at baseline. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

    Measured: before vaccination

  5. Lymphocyte Proliferation as a Measure of Cellular Immune Response in The Study Population Versus the Control Group After Second Vaccination

    Data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE antigen 7 days after the second vaccination. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

    Measured: 7 days after second vaccination

  6. Lymphocyte Proliferation as a Measure of Celluar Immune Response in the Study Population Versus the Control Group After Third Vaccination

    Data for lymphocyte proliferation was detected by thymidine incorporation assay after stimulation with albumin-free TBE antigen 7 days after the third vaccination. Data was standardized based on unstimulated controls of each participant. The stimulation index is given. The stimulation index is the ratio of the number of proliferating lymphocytes with thymidine incorporation in the presence of antigen to that in absence of antigen. A SI value equal or greater to 3.0 represents relevant lymphocyte proliferation, whereas a SI value <3.0 represents no relevant lymphocyte proliferation.

    Measured: 7 days after Third Vaccination

  7. Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Second Vaccination

    Determination of secreted IL13 cytokine levels was performed using the Luminex System 7 days after second vaccination. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

    Measured: 7 days after second vaccination

  8. Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Third Vaccination

    Determination of secreted IL13 cytokine levels was performed using the Luminex System 7 days after third vaccination. Data was standardized based on unstimulated controls of each patient. The fold induction in the presence of TBE antigen to that in absence is given.

    Measured: 7 days after third vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2013 (estimated)
  2. Study startJul 2014
  3. Primary completion28 Oct 2018
  4. Study completion28 Oct 2018

Resources

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
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01991067
Sponsor's protocol ID
EudraCT_2011-002928-41
Status last verified
Jan 2022
First submitted
6 Nov 2013
Last updated
3 Feb 2022
Data monitoring committee
Yes

Publications

  • Harrison N, Grabmeier-Pfistershammer K, Graf A, Schwarzinger I, Aberle JH, Stiasny K, Greinix H, Rabitsch W, Kalhs P, Ramharter M, Burgmann H, Forstner C. Humoral immune response to tick-borne encephalitis vaccination in allogeneic blood and marrow graft recipients. NPJ Vaccines. 2020 Jul 24;5(1):67. doi: 10.1038/s41541-020-00215-1. eCollection 2020.

    PubMed 32728481

  • Harrison N, Grabmeier-Pfistershammer K, Graf A, Trapin D, Tauber P, Aberle JH, Stiasny K, Schmidt R, Greinix H, Rabitsch W, Ramharter M, Burgmann H, Pickl WF, Bahrs C. Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination. Vaccines (Basel). 2021 Aug 15;9(8):908. doi: 10.3390/vaccines9080908.

    PubMed 34452033

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TBE virus vaccine in people with Tick Borne Encephalitis, run by Medical University of Vienna at 1 site in Austria.

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 6 inclusion and 8 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 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Outcome of the Neutralization Test (Number of Subjects With Antibody Response Measured by Neutralization Assay) (time frame: four weeks after the second vaccination). 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 NCT01991067, which also lists 2 linked publications.

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 3 Feb 2022.

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