A Phase 2 interventional study of TBE virus vaccine in Tick Borne Encephalitis, sponsored by Medical University of Vienna. Completed at 1 site in Austria. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-02-03.
Sponsored by Medical University of Vienna · Phase 2, Interventional, and Prevention
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.
51 studies on the registry are indexed under Encephalitis, Tick-Borne; 9 are open to participants now.
This study's enrollment of 34 is below the median of 192 across 32 interventional studies indexed under Encephalitis, Tick-Borne.
Browse Encephalitis, Tick-Borne studies →Medical University of Vienna is the lead sponsor of 1,109 studies on the registry; 184 are open to participants now.
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Male and female subjects will be eligible for participation in this study if they:
Exclusion Criteria:
Subjects will be excluded from participation in this study if they:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Study 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).
Biological: TBE virus vaccine
Clinical 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).
Biological: TBE virus vaccine
TBE virus vaccine FSME Immun is used in both arms for the study population and the control group
Also known as: FSME Immun
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
Time frame: four weeks after the second vaccination
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
Time frame: comparison between baseline and four weeks after second vaccination
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
Time frame: between baseline and four weeks after the third vaccination
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.
Time frame: before vaccination
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.
Time frame: before vaccination
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.
Time frame: 7 days after second vaccination
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.
Time frame: 7 days after Third Vaccination
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.
Time frame: 7 days after second vaccination
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.
Time frame: 7 days after third vaccination
| Milestone | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Started | 19 | 15 |
| Completed | 13 | 10 |
| Not completed | 6 | 5 |
| Withdrew: Lost to follow-up | 6 | 5 |
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
| Participants | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Outcome of the Neutralization Test (Number of Subjects With Antibody Response Measured by Neutralization Assay) | 6 | 14 |
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
| Participants | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Antibody Response as Measured by TBE-ELISA After Second Vaccination | 9 | 14 |
Geometric mean fold change of NT titer between baseline and four weeks after third vaccination was compared between HSCT patients and healthy controls
| Geometric mean fold change | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Change of Antibody Concentration of NT Titer | 3.9 (1.3 to 11.9) | 45.2 (17.5 to 117.0) |
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.
| stimulation index | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Lymphocyte Proliferation as a Measure of Cellular Immune Response in the Study Population Versus the Control Group Prior Vaccination | 4.2 (1.02 to 69.7) | 0.9 (0.61 to 2.37) |
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.
| fold induction | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Fold Induction in IL13 Cytokine Levels Before Vaccination (Baseline) in the Study Population Versus the Control Group | 1.0 (0.96 to 98.93) | 0.61 (0.57 to 0.84) |
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.
| stimulation index | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Lymphocyte Proliferation as a Measure of Cellular Immune Response in The Study Population Versus the Control Group After Second Vaccination | 8.4 (0.7 to 76.6) | 8.3 (1.8 to 23.9) |
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.
| stimulation index | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Lymphocyte Proliferation as a Measure of Celluar Immune Response in the Study Population Versus the Control Group After Third Vaccination | 21.0 (0.8 to 109.3) | 13.0 (1.8 to 27.8) |
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.
| fold induction | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Second Vaccination | 5.6 (1.0 to 180.5) | 2.1 (0.6 to 5.9) |
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.
| fold induction | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| Fold Induction in IL13 Cytokine Levels in the Study Population Versus the Control Group After Third Vaccination | 32.3 (0.5 to 153.8) | 3.4 (0.6 to 7.2) |
Collected over Adverse events were collected during the whole study period from enrollment to four weeks after third vaccination (Day 298-393 corresponds to 4 weeks after third vaccination). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| HSCT Patients / TBE Virus Vaccine | 0/19 (0%) | 4/19 (21.1%) | 15/19 (78.9%) |
| Healthy Volunteers / TBE Virus Vaccine | 0/15 (0%) | 0/15 (0%) | 6/15 (40%) |
| Event | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| cholecystolithiasisHepatobiliary disorders | 1/19 | 0/15 |
| haemometraReproductive system and breast disorders | 1/19 | 0/15 |
| influenzaInfections and infestations | 1/19 | 0/15 |
| acute myeloid leukemiaBlood and lymphatic system disorders | 1/19 | 0/15 |
| Event | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine |
|---|---|---|
| local pressure painSkin and subcutaneous tissue disorders | 9/19 | 5/15 |
| headacheNervous system disorders | 3/19 | 0/15 |
| local swellingSkin and subcutaneous tissue disorders | 2/19 | 0/15 |
| shiveringGeneral disorders | 2/19 | 1/15 |
| fatigueGeneral disorders | 2/19 | 1/15 |
| nauseaGastrointestinal disorders | 2/19 | 0/15 |
| cold-like symptomsGeneral disorders | 2/19 | 0/15 |
| swelling of parotid glandEndocrine disorders | 0/19 | 1/15 |
| local rednessSkin and subcutaneous tissue disorders | 1/19 | 0/15 |
| local indurationSkin and subcutaneous tissue disorders | 1/19 | 0/15 |
| Age, Continuous(years) | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine | Total |
|---|---|---|---|
| Median | 31 (22 to 61) | 30 (21 to 60) | 30.5 (21 to 61) |
| Sex: Female, Male(Participants) | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine | Total |
|---|---|---|---|
| Female | 8 | 6 | 14 |
| Male | 11 | 9 | 20 |
| Race and Ethnicity Not Collected(Participants) | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine | Total |
|---|---|---|---|
| Austria | 19 | 15 | 34 |
| Body mass index(kg/m^2) | HSCT Patients / TBE Virus Vaccine | Healthy Volunteers / TBE Virus Vaccine | Total |
|---|---|---|---|
| Median | 26.9 (19.5 to 39.1) | 22.2 (18.5 to 30.3) | 24.2 (18.5 to 39.1) |
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