Efficacy and Safety in Imlifidase Desensitized Kidney Tx Patients, Including Two Non-Comparative Reference Cohorts

After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry. All highly sensitized ESRD patients with a positive XM will be desensitized with imlifidase to convert the XM to negative and then transplanted. Following transplantation, patients will receive induction therapies (corticosteroids, rabbit anti-human thymocyte immunoglobulin (rATG)), rejection prophylaxis (high-dose intravenous immunoglobulin (IVIg), rituximab or biosimilar) and maintenance immunosuppressive therapies. The patients will be followed for 12 months.

The efficacy of imlifidase per se, i.e. rapidly cleavage of IgG to enable transplantation, is not reflected by the important clinical outcomes 1-year graft failure-free survival and kidney function. These are instead a measure of effectiveness and safety in the real-world transplantation setting. It should be noted that patient outcome is highly dependent on the post-transplantation management, as well as compliance to maintenance immunosuppressive therapy.

All patients with donor specific antibodies (DSAs) are at risk for antibody-mediated reactions (AMRs). Imlifidase removes DSA quickly and efficiently at the time of transplantation but, as with other desensitization methods, the antibodies are expected to re-occur after transplantation. The highly sensitized patients included in this trial must therefore be closely monitored for any signs of AMR. Protocol kidney biopsies will be performed at 6 months and 1 year after transplantation. For-cause biopsies, DSA and estimated glomerular filtration rate (eGFR) will be collected to assess AMR frequency.

A non-comparative concurrent reference cohort consisting of kidney transplanted patients from participating trial sites with any grade of sensitization and a negative XM towards their donor will be included in the trial to address differences in-site practice, experience, and amount of immunosuppressive therapies given that may have an impact on the overall results for the imlifidase-treated cohort. Once a highly sensitized imlifidase treated patient has been transplanted at a site, subsequent patients who are offered a compatible kidney will be offered the opportunity to be included in the trial as part of the reference cohort group and transplanted. The goal is to have at least 1 or 2 patients from each site participating in the non-comparative concurrent reference cohort. Given that the patients in this cohort will be qualitatively different from the imlifidase treated patients, formal statistical comparisons will not be appropriate. Patients included in the non-comparative concurrent reference cohort will be followed for 12 months after transplantation and treated in accordance with each clinic's normal transplantation routines.