E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination against SARS-CoV-2 in patients with immunosuppressive therapy or immunodeficiencies |
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E.1.1.1 | Medical condition in easily understood language |
Vaccination against Covid-19 in patients who are under medication which suppresses the immune system or have immunodeficiencies |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
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. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 1500 U/ml of SARS-CoV-2 antibodies 4 weeks after second mRNA vaccination (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, or external routine evaluation of humoral response) 5. A maximum of 12 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 b) Male and female healthy controls will be eligible for participation in this study if they: 1. Are ≥18 years on the day of screening 2. Received two doses of SARS-CoV-2 (Biontech/Pfizer, Moderna) vaccine according to recommendations in the label and/or national guidelines. 3. Did develop < 1500 U/ml of SARS-CoV-2 antibodies 4 weeks after second mRNA vaccination 4. A maximum of 12 months after second vaccination 5. Have an understanding of the study, agree to its provisions, and give written informed consent before study entry 6. 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 |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
A) 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). B) The efficacy of a 3rd mRNA boost vaccination in immunocompromised patients with inadequate humoral response (antibody titre <1500U/ml) to standard SARS-CoV-2 vaccination will be compared to low titre heathy controls by assessing the difference in antibody titre change before and after a second boost between the two groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after SARS-CoV-2 vaccination |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
one week and four weeks after SARS-CoV-2 vaccination |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part A) single blind randomized control trial; Part B) open label trial |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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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last visit of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |