Intervention A - vaccination Patients following kidney transplant recipients who do not have an adequate immune response against SARS-CoV-2 following two doses of an mRNA vaccine Substudy A: kidney transplant recipients who did not develop antibodies after a fourth dose Intervention B - monoclonal antibodies Kidney transpant recipients who do not develop neutralizing antibodies after at least two doses of SARS-CoV-2 vaccine
Conditions
Interventions
Trade Name: COVID-19 Vaccine Janssen
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein (Ad26.COV2-S)
Other descriptive na
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Intervention A: • patient has received a kidney transplantation • full SARS-CoV-2 vaccination with mRNA vaccine (two doses) at least 4 weeks before screening • > 18 years of age • no SARS-CoV-2 spike protein antibodies at least 4 weeks after the second dose of an mRNA vaccine Substudy A: • no SARS-CoV-2 spike protein antibodies four weeks after the third dose • Maintenance immunosuppression with mycophenolate or azathioprine Intervention B: • Participant has received a kidney transplantation. • Participant has received at least two doses of a SARS-CoV-2 vaccine. • > 18 years of age. • No neutralizing SARS-CoV-2 antibodies at least 4 weeks after the last dose of any SARS-CoV-2 vaccine. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Intervention A: • acute illness with fever • Prior documented infection with SARS-CoV-2 • triple anticoagulation therapy • Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s) • Subject has known sensitivity or intolerance to any of the products to be administered for the purpose of this study • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures • Subject is pregnant or breast feeding Substudy A: • SARS-CoV-2 spike protein antibodies four weeks after the 3rd vaccination > 0.8 U/mL Intervention B: • Prior documented infection with SARS-CoV-2. • Triple anticoagulation therapy. • Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s). • Subject has known sensitivity or intolerance to any of the products to be administered for the purpose of this study. • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures. • Subject is pregnant or breast feeding. • Prior receipt of any mAbs against COVID19 (licensed or investigational) =30 days before enrolment. • Administration of immunoglobulins =30 days before enrolment. • Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Intervention A: To evaluate if a switch to a vector-based vaccine improves immunological response (ie. development of antibodies) against SARS-CoV-2 in kidney transplant recipients compared to a third dose of the previously applied mRNA vaccine Substudy A: to test if reduction of maintenance immunosuppression results in a better response to the fourth vaccine Intervention B: Pharmacokinetics of AZD7442 in kidney transplant recipients;Secondary Objective: Intervention A: To evaluate the cellular immune response against SARS-CoV-2 following vaccination Intervention B: Neutralizing capacity against SARS-CoV-2 following administration of AZD7442;Primary end point(s): Intervention A: Number of patients presenting a positive humoral immune response (antibody) at 4 weeks after the third vaccination SubstudyA: atients presenting a positive humoral immune response (antibody) at 4 weeks after the fourth vaccination Intervention B: AZD7442 plasma levels over 12 months;Timepoint(s) of evaluation of this end point: Intervention A: Visit 3 at 4 weeks after vaccination for primary endpoint Substudy A: Substudy_A_Visit_5 at 4 weeks after vaccination for primary endpoint Intervention B: Visit 9 at 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Intervention A: - Number of patients presenting a positive humoral immune response (antibody) at 8, 12, 24 and 48 weeks after vaccination - Number of detectable antibodies (U/ml measured by the Roche ELISA test) at 4, 8, 12,24 and 48 weeks after vaccination - Number of patients presenting a positive cellular immune response defined as doubling of extracellular IFNg concentration in the plasma after ex-vivo re-stimulation with a SARS-CoV-2 spike protein peptide pool at 4 weeks after the vaccination - Strength of the cellular response to SARS-CoV-2 spike protein peptides measured in terms of the extracellular IFNg concentration after ex-vivo re-stimulation with a peptide pool at 4 weeks after the vaccination. - iIncidence of COVID-19 disease within 24 and 48 months after vaccination Substudy A: - Number and percentage of patients presenting a positive humoral immune response at Substudy_A_day_15 (i.e. 7 days after the 4th vaccination). Intervention B: • Local and systemic adverse events will be assessed by post immunization diary cards at 2, 4, 8, 12, 24, 36 and 48 weeks. • Neutralizing capacity of patient serum samples at 2, 4, 8,12,24, 36, and 48 weeks. • Number of patients with AZD 7442 serum levels < 2.1µl/ml at 2, 4, 8,12,24, 36, and 48 weeks • SARS-CoV- spike protein antibodies at 2, 4, 8,12,24, 36, and 48 weeks. • SARS-CoV-2 infection at 2, 4, 8,12,24, 36, and 48 weeks assessed by SARS-CoV-2 nucleocapsid antibodies and patient history (positive PCR test). • Hospitalization or death from COVID-19. • Humoral and cellular immune response to additional SARS-CoV-2 vaccination (at 4 weeks after boost vaccination) in patients on AZD 7442 treatment (additional vaccination is not a study intervention (observational); response rate will be compared to patients not receiving AZD 7442 [results from the BOOST-TX study]). Cellular response will be assessed by ELISPOT (SARS-CoV-2 spike protein-specific). • Alloimmune response assessed by Donor-speci | — |
Countries
Austria
Contacts
Public ContactRoman Reindl-Schwaighofer
Medical University of Vienna
Outcome results
None listed