Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

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Brief Title

Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

Official Title

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

Brief 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. 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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Antibody Response as Measured by TBE-ELISA After Second Vaccination

Condition

Tick Borne Encephalitis

Intervention

TBE virus vaccine

Study Arms / Comparison Groups

 HSCT patients / TBE virus vaccine
Description:  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).

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

34

Start Date

July 2014

Completion Date

October 28, 2018

Primary Completion Date

October 28, 2018

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Christina Forstner, MD, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT01991067

Organization ID

EudraCT_2011-002928-41


Responsible Party

Principal Investigator

Study Sponsor

Medical University of Vienna

Collaborators

 Austrian Science Fund (FWF)

Study Sponsor

Christina Forstner, MD, Principal Investigator, Medical University of Vienna


Verification Date

July 2020