E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Characterization of humoral and cellular immunity for tick-borne encephalitis (TBE) vaccination in allogeneic blood and marrow graft recipients: a pilot study
Study group consists of patients 11 to 13 months after allogeneic stem cell transplantation
Control group consists of healthy volunteers without previous TBE vaccination |
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E.1.1.1 | Medical condition in easily understood language |
Characterization of humoral and cellular immunity for tick-borne encephalitis (TBE) vaccination in allogeneic blood and marrow graft recipients: a pilot study |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the humoral immunogenicity to a TBE vaccination in allogeneic blood and marrow graft (HSCT) recipients compared to healthy volunteers without previous TBE vaccination, by measuring the quantitative antibody levels using neutralization test (NT) and enzyme-linked immunosorbent assay test (ELISA) |
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E.2.2 | Secondary objectives of the trial |
-To assess cellular immunogenicity of the TBE vaccination in allogeneic HSCT recipients, by measuring the lymphocyte proliferation and cytokine levels after in vitro stimulation with peripheral blood mononuclear cells with whole aluminium hydroxide-free and human albumin-free TBE antigen
-To assess the immune status in HSCT recipients prior to and after vaccination, as measured by quantitative immunoglobulin levels and by immunofluorescence staining of peripheral blood T and B lymphocytes and flow cytometry analyses |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients ≥18 years who
-had undergone an allogeneic HSCT 11 to 13 months ago or
-healthy volunteers without previous TBE vaccination |
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E.4 | Principal exclusion criteria |
-Previous TBE vaccination following HSCT
-HSCT patients with extremely severe acute graft versus host disease (receiving prednisone >0.5 mg/kg bodyweight as part of a combination therapy or a three agent immunosuppressive treatment)
-Previous TBE virus infection, previous dengue virus infection or vaccination against yellow fever or Japanese encephalitis
-Any acute febrile illness in the 2 weeks prior to or at the time of enrolment
-A history of severe allergic reactions or anaphylaxis after vaccination
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-If female, are pregnant or lactating
-If belonging to the healthy control group are immunosuppressed |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the immunogenicity of the TBE vaccination in allogeneic HSCT recipients compared to the healthy volunteers without previous TBE vaccination, the outcome of the neutralization test (NT) will be assessed four weeks after the second vaccination. Therefore, the number of subjects with NT titers against TBE virus >10 (=seroconversion rate), assumed to be the threshold for antibody-mediated protection, will be evaluated. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Antibody concentrations of TBE ELISA (validated in-house test, Department of Virology, Medical University of Vienna) before and four weeks after the second and third vaccination.
o Increase of antibody response.
o Number of subjects with seroconversion defined when patients reach antibody levels above the cut-off of TBE ELISA.
• Antibody concentrations of NT titers after the third vaccination compared to the second vaccination.
o Increase of antibody response.
o Number of subjects with NT titers against TBE virus >10.
• Evaluation of cellular immunity before and one week after the second and third vaccination.
o by measuring lymphocyte proliferation after in vitro stimulation with peripheral blood mononuclear cells with whole aluminium hydroxide-free and human albumin-free TBE antigen
o by measuring of cytokines after in vitro stimulation with peripheral blood mononuclear cells with whole aluminium hydroxide-free and human albumin-free TBE antigen
• Evaluation of immune reconstitution and quantitative immunoglobulin levels at baseline and every following 12 weeks throughout the study in HSCT recipients only.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
effectiveness of humoral and cellular immunity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial = if 26 HSCT patients in the study group and 26 healthy volunteers in the control group will have completed the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |