Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

NCT ID: NCT01991067

Last Updated: 2022-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-10-28

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.

Conditions

Tick Borne Encephalitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

TBE virus vaccine

Intervention Type: BIOLOGICAL

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

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).

Group Type: ACTIVE_COMPARATOR

TBE virus vaccine

Intervention Type: BIOLOGICAL

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

Interventions

TBE virus vaccine

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

Intervention Type: BIOLOGICAL

Other Intervention Names

FSME Immun

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Christina Forstner, MD

Associate Professor, PD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christina Forstner, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

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

Vienna, , Austria

Countries

Austria

References

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.

Reference Type: RESULT

PMID: 32728481 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34452033 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

EudraCT_2011-002928-41

Identifier Type: -

Identifier Source: org_study_id