| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients following kidney transplant recipients who do not have an adequate immune response against SARS-CoV-2 following vaccination |
|
| 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 |
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 |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
|
|
| E.4 | Principal 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.
|
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | 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 |
|
| E.5.2 | 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-specific HLA antibodies (humoral alloimmunity, n=200 at week 24 and 48) and donor-specific T-cells using donor-specific ELISPOT assays in up to 40 patients with available donor cells (since 2016 PBMCs of local organ donors are routinely stored in liquid nitrogen at time of transplantation).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Intervention A:
antibody response 8, 12, 24 and 48 weeks after vaccination
T-cell response at 4 weeks
SARS-CoV-2 infection 24 and 48 weeks
Intervention B:
neutralizing antibodies at 2,4,8,12,24,36 and 48 weeks
local and systemic side effects of injection "tolerability": 2 and 4 weeks |
|
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Intervention B is a prospective observational study |
|
| 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 | 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
|
|
| 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 | 12 |
| E.8.9.1 | In the Member State concerned days | |
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