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

Prior treatment

• Use of investigational agents within 5 terminal elimination half-lives prior to the transplantation
• Malignancy within 5 years prior to transplantation
• Previous treatment with imlifidase
• Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment
• Female of childbearing potential, not willing to use effective contraception during the 3 weeks following treatment with imlifidase. In the context of this trial, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; (i) oral, (ii) intravaginal, or (iii) transdermal
  • progestogen-only hormonal contraception associated with inhibition of ovulation; (i) oral, (ii) injectable, or (iii) implantable
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system (IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • true abstinence: When this is in line with the preferred and usual lifestyle of the patient. \[Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]
• Any other reason that, in the view of the investigator, precludes transplantation
• Patients treated with mammalian target of rapamycin (mTOR) inhibitors
• Patients treated with belatacept

Other illness

• Positive serology for human immunodeficiency virus (HIV)
• Clinically relevant active infection(s) as judged by the investigator
• Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test
• Hypersensitivity to the active substance (imlifidase) or to any of the excipients
• Ongoing serious infections
• Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
• Severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent respiratory disease

Other

• Contemporaneous participation in medical device studies
• Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities
• Inability by the judgement of the investigator to participate in the trial for any other reason
• Breast feeding or pregnancy

• Male or female patient aged 18-75 years
• ABO-compatible deceased donor aged 10-70 years
• ESRD active on the renal transplant waiting list of a kidney allocation system at the time of screening
• High sensitization with the highest unmet medical need unlikely to be transplanted under the available kidney allocation system including prioritisation programmes for highly sensitized patients
• Known DSA against an available deceased donor
• Positive crossmatch test determined by complement-dependent cytotoxicity crossmatch (CDCXM) and/or flow cytometric crossmatch (FCXM) against an available deceased donor. If physical XM tests are not practically possible due to lack of time, patients may be included on a virtual crossmatch (vXM) predictive of a positive XM test.
• Signed Informed Consent obtained before any trial-related procedures
• Willingness and ability to comply with the protocol
• Active on the renal transplant waiting list at a participating trial site at the time of screening
• An acceptable kidney transplant from a deceased donor
• Signed Informed Consent obtained before any trial related procedures
• Willingness and ability to comply with the protocol
• ESRD with a kidney transplant from a deceased donor
• Being transplanted in Europe after 01-Jan-2010 and included in the CTS registry
• Panel reactive antibodies (PRA) ≥ 50% (CDC T- or B-cell PRA, calculated panel reactive antibodies (cPRA), or virtual panel reactive antibodies (vPRA))
• Maintenance immunosuppression (intention to treat) with calcineurin inhibitor, mycophenolate mofetil (MMF) and corticosteroids in combination