Survival and Dialysis Independency in Highly Sensitized Patients After Desensitization With Imlifidase and Tx of Kidneys

Study Overview
=================
Brief Summary
-----------------
The goal of this follow-up study is to learn about long-term patient survival and graft function in highly sensitized patients who have received desensitization treatment with imlifidase or standard of care (SoC) in order to enable kidney transplantation in clinical study ConfIdeS (20-HMedIdeS-17, NCT04935177).

Detailed Description
-----------------
This is an observational follow-up study subsequent to the ConfIdeS study (20-HMedIdeS-17, NCT04935177) in highly sensitized patients who were randomized to imlifidase or SoC desensitization prior to kidney transplantation with a deceased donor graft, or, if SoC perioperative treatment has been deemed not appropriate, wait for a more immunologically compatible organ offer. After the patients have given written informed consent to participate in the follow-up they will be included in the study and followed until 5 years after randomization in the ConfIdeS study. Most of the assessments in this study are already part of the follow up within SoC for these patients. During the local clinic routine follow-up visits at year 2, 3 and 5 after randomization in the ConfIdeS study, information about patient survival, wait-list status, graft survival, kidney function, and health related quality of life will be evaluated.

Official Title
-----------------
A Prospective, Long-term Confirmatory Follow up Trial in Highly Sensitized Patients Treated With Imlifidase or Standard of Care in the ConfIdeS (20-HMedIdeS-17) Trial

Conditions
-----------------
Kidney Transplantation in Highly Sensitized Patients

Intervention / Treatment
-----------------
* Drug: Imlifidase administered in the ConfIdeS study
* Other: Best available treatment administered in the ConfIdeS study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed Consent obtained before any trial-related procedures. Previous participation in the clinical trial ConfIdeS. Exclusion Criteria: 1. Inability by the judgement of the investigator to participate in the trial for any reason.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Imlifidase administered in the ConfIdeS study<br> | Drug: Imlifidase administered in the ConfIdeS study<br>* Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc- fragment and efficiently neutralizes Fc-mediated activities of IgG.<br>* Other names: IdeS, HMED-IdeS;|
| Best available treatment administered in the ConfIdeS study<br> | Other: Best available treatment administered in the ConfIdeS study<br>* Institution-specific desensitization treatment prior to kidney transplantation in the ConfIdeS study OR remain on wait list for a more compatible organ offer if desensitization with institutional protocol is not appropriate<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and free of dialysis at 3 years |  | 3 years after randomization in the ConfIdeS study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients alive and free of dialysis at 5 years |  | 5 years after randomization in the ConfIdeS study | 
| Proportion of patients alive at 3 and 5 years |  | 3 and 5 years after randomization in the ConfIdeS study | 
| Graft failure-free survival rates at 3 and 5 years | Graft failure-free survival is defined as time from randomization to the fist of either graft failure or death | 3 and 5 years after randomization in the ConfIdeS study | 
| Graft survival rates at 3 and 5 years | To be assessed in patients who were transplanted at randomization in the ConfIdeS study | 3 and 5 years after randomization in the ConfIdeS study | 
| Number of patients per wait-list category | The different wait-list categories are: transplanted, active, temporary inactive, inactive, or deceased | 3 and 5 years after randomization in the ConfIdeS study | 
| Mean estimated glomerular filtration rate (eGFR) at 3 and 5 years | eGFR is a measure of kidney function. eGFR will be calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. Kidney disease is characterised by a decreased eGFR value. eGFR will be set to zero, for randomized patients who do not undergo transplantation, lose their graft or die. | 3 and 5 years after randomization in the ConfIdeS study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Desensitization, Highly sensitized, Positive crossmatch, Unlikely to be transplanted, Renal transplantation, Deceased donor