|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Vaccination against SARS-CoV-2 in patients with rituximab therapy
|Medical condition in easily understood language
| Rituximab has been shown to impair humoral responses to various vaccines including SARS-CoV-2 vaccination.
|Diseases [C] - Immune System Diseases [C20]
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The study aims to investigate the humoral and cellular immune responses after a second boost vaccination with either an mRNA or an vector vaccine against SARS-CoV-2 in adult patients treated with rituximab who did not develop antibodies 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 rituximab by measuring quantitative antibody levels by enzyme-linked immunosorbent assay test (ELISA) and neutralization test (NT) or pseudo viral neutralization assay.
There is no statistical difference in the seroconversion rate between patients receiving a third mRNA vaccination and the patients receiving a second boost with AstraZeneca.
|Secondary objectives of the trial
To compare cellular immunogenicity of the third mRNA SARS-Cov-2 vaccination will be compared to patients receiving AstraZeneca vaccination as second boost in immunosuppressed patients. 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.
To assess safety of a second boost vaccination.
To evaluate the influence of vaccination on underlying disease activity.
|Trial contains a sub-study
|Principal inclusion criteria
Male and female subjects will be eligible for participation in this study if they:
1. Are ≥18 years on the day of screening
2. Have a chronic condition and have been treated with a B-cell depleting therapy (rituximab) within the last 12 months
3. Received mRNA SARS-CoV-2 (Biontech/Pfizer or Moderna) vaccine
4. Did not develop humoral immunity 4 weeks after second mRNA vaccination to SARS-CoV-2 (analyzed during the study “Characterization of immune responsiveness after mRNA SARS-CoV-2 Vaccination in patients with immunodeficiency or immunosuppressive therapy”, EK-Nr. 1073/2021, EudraCT Nr. 2021-000291-11)
5. A maximum of 6 months after second vaccination
6. Have an understanding of the study, agree to its provisions, and give written informed consent before study entry
7. 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
|Principal exclusion criteria
Subjects will be excluded from participation in this study if they:
1. Have shown humoral response 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 study compounds
6. Urgent need for next rituximab application
|E.5 End points
|Primary end point(s)
|Primary study endpoint
Difference in SARS-CoV-2 antibody seroconversion rate by week 4 after vaccination boost at baseline between 3rd mRNA SARS-CoV-2 (Biontech/Pfizer or Moderna) and vector SARS-CoV-2 vaccine (AstraZeneca).
|Timepoint(s) of evaluation of this end point
|4 weeks after SARS-CoV-2 vaccination
|Secondary end point(s)
|Secondary study endpoints:
The secondary endpoints of this study are:
Overall SARS-Cov-2 antibody seroconversion rate by week 4 after vaccination boost at baseline
Difference in overall SARS-Cov-2 antibody seroconversion rate by week 4 after vaccination boost at baseline between patient with and without B-cell repopulation.
Antibody concentrations of SARS-CoV-2 ELISA 4 weeks after vaccination boost at baseline.
Effect of immunosuppressive comedication on SARS-Cov-2 antibody seroconversion rate by week 4 after vaccination boost at baseline
Evaluation of cellular immunity before and one week after the vaccination.
Safety of vaccination boost.
|Timepoint(s) of evaluation of this end point
|one week and four weeks after SARS-CoV-2 vaccination
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|last visit of the last subject
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial days