Vaccination against SARS-CoV-2 in patients with immunosuppressive therapy or immunodeficiencies
Conditions
Sponsors
Medical University of Vienna, Department for Internal Medicine III, Division of Rheumatology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Male and female patients will be eligible for participation in this study if they: 1. Are =18 years on the day of screening 2. Being immunocompromised (either primary or secondary immunodeficiency or been treated with immunosuppressive therapy within the last 12 months Immunosuppressive therapies include glucocorticoids, cytostatics, antibodies, drugs acting on immunophilins and other treatments like interferons and TNF binding proteins and exclude patients under B cell depleting therapy (like Rituximab, Ocrelicumab, Ofatumumab, Epratuzumab or Obinutuzumab) 3. Received two doses of SARS-CoV-2 (Biontech/Pfizer, Moderna) vaccine according to recommendations in the label and/or national guidelines. 4. Did develop =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: Subjects will be excluded from participation in this study if they: 1. Have shown humoral response (> 1500 U/ml) to the SARS-CoV-2 vaccination 2. Had grade 3 adverse effects from the mRNA vaccination reported 3. Pregnancy and breast feeding 4. Signs of SARS-CoV-2 infection (including previous positive PCR testing) 5. Any other contraindication to any of the vaccine compounds 6. For healthy controls: diagnosis of chronic inflammatory condition including primary or secondary immunodeficiency or ever receiving immunosuppressing therapy as stated above
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study aims to investigate A) the humoral and cellular immune responses after a second boost vaccination against SARS-CoV-2 in adult patients treated with immunosuppressive therapy who did not show response to the first two vaccinations with an mRNA vaccine. To assess the immunogenicity to a third vaccination mRNA-SARS-CoV-2 vaccine (Biontech/Pfizer or Moderna) compared to a vector SARS-CoV-2 (AstraZeneca) vaccination as a second boost in patients with immunosuppressive therapy. B) To compare the immunogenicity to a third vaccination with a mRNA-SARS-CoV-2 vaccine as a second boost in immunocompromised patients and healthy controls who developed insufficient titres of antibodies (< 1500 U/ml) after the standard vaccination by measuring quantitative antibody levels by spike-protein-based assay. The level of antibody increase will be compared between the two groups.;Secondary Objective: • Cellular immunogenicity of the third mRNA SARS-CoV-2 vaccination will be compared to patients receiving a vector vaccination as second boost in immunocompromised patients without prior humoral response. Further, T cell responses will be compared in immunocompromised patients as well as healthy controls before and after a second mRNA boost vaccination. T cell proliferation will be assessed, and T-cell cytokine expression will be measured using flow-cytometry following in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with SARS-CoV-2 specific antigens. • Comparison of total antibody titre after the second boost as well as absolute and relative change in antibody titre before and after the second boost in immunosuppressed patients versus the healthy controls • To assess safety of a second boost vaccination. • To qualitatively evaluate the influence of a second boost vaccination on underlying disease treated with immunosuppressive therapy. ;Primary end point(s): A) Difference in SARS-CoV-2 antibody seroconversion rate by week 4 after vaccination boo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: • Overall SARS-CoV-2 antibody seroconversion rate by week 4 after vaccination boost in patients with no detectable antibodies at baseline • Antibody concentrations including neutralizing antibodies against SARS-CoV-2 4 weeks after vaccination boost at baseline • Difference in absolute and relative change of antibody titres before and after second mRNA vaccine boost between patients and healthy controls • Effect of disease entity on SARS-CoV-2 antibody seroconversion rate and titre changes by week 4 after vaccination boost at baseline • Effect of immunosuppressive medication and steroids on SARS-CoV-2 antibody seroconversion rate/titre change by week 4 after vaccination boost at baseline • Effect of patient characteristics (age, gender, time between second and third vaccination) on seroconversion rate/titre change by week 4 after vaccination boost at baseline • Evaluation of cellular immunity before and one week after the vaccination in all groups • Safety of vaccination boost (all groups) • Effect of vaccination on disease activity of underlying rheumatic disease;Timepoint(s) of evaluation of this end point: one week and four weeks after SARS-CoV-2 vaccination | — |
Countries
Austria
Contacts
Public ContactClinical Trials Office
Medical University of Vienna
Outcome results
None listed