Humoral and Cellular Immunity for TBE Vaccination in Allogeneic HSCT Recipients

NCT01991067 | Completed Phase 2 Results DMC

• 1 other identifier: EudraCT_2011-002928-41
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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

Keywords

Marrow transplant recipients

Outcome Measures

Primary Outcomes (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

  four weeks after the second vaccination

Secondary Outcomes (8)

• Antibody Response as Measured by TBE-ELISA After Second Vaccination

  comparison between baseline and four weeks after second vaccination

• Change of Antibody Concentration of NT Titer

  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

  before vaccination

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

  before vaccination

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

  7 days after second vaccination

Study Arms (2)

HSCT patients / TBE virus vaccine

ACTIVE COMPARATOR

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

healthy volunteers / TBE virus vaccine

ACTIVE COMPARATOR

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

Interventions

TBE virus vaccine BIOLOGICAL

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

Also known as: FSME Immun

HSCT patients / TBE virus vaccine; healthy volunteers / TBE virus vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University of Vienna: lead
• Austrian Science Fund (FWF): collaborator

Study Sites (1)

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

Vienna, 1090, Austria

Location

Related Publications (2)

• 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.

  PMID: 32728481 RESULT

• 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.

  PMID: 34452033 RESULT

MeSH Terms

Conditions

Encephalitis, Tick-Borne

Interventions

FSME-IMMUN vaccine

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Tick-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Limitations and Caveats

A limitation of this study might be the definition of response to vaccination. As the majority of HSCT patients had pre-existing antibodies, the concept of seroconversion was not applicable. Instead, a 2-fold rise in NT titer was used as outcome.

Results Point of Contact

• Title: Assoc. Prof. Dr. Christina Bahrs
• Organization: Medical University of Vienna, Department of Medicine I, Division of Infectious Diseases

christina.a.forstner@meduniwien.ac.at

+4314040044400

Study Officials

• Christina Forstner, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, PD

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 25, 2013
• Study Start: July 1, 2014
• Primary Completion: October 28, 2018
• Study Completion: October 28, 2018
• Last Updated: February 3, 2022
• Results First Posted: July 14, 2020

Record last verified: 2022-01

Locations

AU (1)