Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Medical University of Vienna
Sponsor:
Collaborator:
Austrian Science Fund (FWF)
Information provided by (Responsible Party):
Christina Forstner, MD, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01991067
First received: November 6, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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 and every twelve weeks throughout the complete study period in HSCT patients only.


Condition Intervention Phase
Tick Borne Encephalitis
Biological: TBE virus vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Characterization of Humoral and Cellular Immunity for Tick-borne Encephalitis (TBE) Vaccination in Allogeneic Blood and Marrow Graft Recipients: a Pilot Study

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Outcome of the neutralization test (number of subjects with neutralization titres against TBE virus >10) [ Time Frame: four weeks after the second vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antibody concentrations of TBE-ELISA [ Time Frame: before vaccination, four weeks after the second and third vaccination ] [ Designated as safety issue: No ]
  • Antibody concentration of NT titres [ Time Frame: four weeks after the third vaccination ] [ Designated as safety issue: No ]
  • Lymphocyte proliferation as a measure of cellular immune response in the study population versus the control group [ Time Frame: before vaccination, one week after the second and third vaccination ] [ Designated as safety issue: No ]
  • quantitative levels of cytokines interleukin 1, interleukin 6, interleukin 10, tumor necrosis factor alpha, interferon gamma as a measure of cellular immune response of study population versus control group [ Time Frame: before vaccination, one week after second and one week after the third vaccination ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: July 2014
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HSCT patients / TBE virus vaccine
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
TBE virus vaccine FSME Immun is used in both arms for the study population and the control group
Other Name: FSME Immun
Active Comparator: healthy volunteers / 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
Other Name: FSME Immun

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01991067

Contacts
Contact: Christina Forstner, MD 0043140400 ext 4440 christina.a.forstner@meduniwien.ac.at
Contact: Heinz Burgmann, MD 0043140400 ext 4440 heinz.burgmann@meduniwien.ac.at

Locations
Austria
Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine Recruiting
Vienna, Austria, 1090
Contact: Christina Forstner, MD    0043140400 ext 4440    christina.a.forstner@meduniwien.ac.at   
Contact: Heinz Burgmann, MD    0043140400 ext 4440    heinz.burgmann@meduniwien.ac.at   
Principal Investigator: Heinz Burgmann, MD         
Sponsors and Collaborators
Medical University of Vienna
Austrian Science Fund (FWF)
Investigators
Principal Investigator: Christina Forstner, MD Medical University of Vienna
  More Information

No publications provided

Responsible Party: Christina Forstner, MD, Assistant Professor, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01991067     History of Changes
Other Study ID Numbers: EudraCT_2011-002928-41
Study First Received: November 6, 2013
Last Updated: July 30, 2014
Health Authority: Austria: Ethikkommission

Keywords provided by Medical University of Vienna:
Marrow transplant recipients

Additional relevant MeSH terms:
Encephalitis
Encephalitis, Tick-Borne
Encephalitis, Arbovirus
Encephalitis, Viral
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Arbovirus Infections
Tick-Borne Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on October 19, 2014