A Controlled, Open-label PA Efficacy and Safety Study in Imlifidase Desensitised Kidney Tx Patients With Positive XM Against a Deceased Donor Prior to Imlifidase Treatment, Including Non-comparative Registry and Concurrent Reference Cohorts

20-HMedIdeS-19

An open-label post authorization efficacy and safety study evaluating graft failure-free survival at 1-year in highly sensitized end-stage renal disease (ESRD) patients with positive crossmatch (XM) against a deceased donor prior to desensitized with imlifidase and subsequent kidney transplantation. Two non-comparative reference cohorts are included to assess the impact of differences in post-transplantation management and outcome in less sensitized patients.

2022-04-19

2024-12-01

2024-12-01

Recruiting

Early phase I

225

Inclusion Criteria: Inclusion criteria for ALL patients 1. Male or female patient aged 18-75 years 2. ABO-compatible deceased donor aged 10-70 years Inclusion criteria for IMLIFIDASE patients 1. ESRD active on the renal transplant waiting list of a kidney allocation system at the time of screening 2. 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 3. Known DSA against an available deceased donor 4. 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. 5. Signed Informed Consent obtained before any trial-related procedures 6. Willingness and ability to comply with the protocol Inclusion criteria for patients in the NON-COMPARATIVE CONCURRENT REFERENCE COHORT 1. Active on the renal transplant waiting list at a participating trial site at the time of screening 2. An acceptable kidney transplant from a deceased donor 3. Signed Informed Consent obtained before any trial related procedures 4. Willingness and ability to comply with the protocol Inclusion criteria for patients in the NON-COMPARATIVE HISTORICAL REFERENCE COHORT 1. ESRD with a kidney transplant from a deceased donor 2. Being transplanted in Europe after 01-Jan-2010 and included in the CTS registry 3. Panel reactive antibodies (PRA) ≥ 50% (CDC T- or B-cell PRA, calculated panel reactive antibodies (cPRA), or virtual panel reactive antibodies (vPRA)) 4. Maintenance immunosuppression (intention to treat) with calcineurin inhibitor, mycophenolate mofetil (MMF) and corticosteroids in combination Exclusion Criteria: Exclusion criteria for IMLIFIDASE patients and for patients in the NON-COMPARATIVE CONCURRENT REFERENCE COHORT 1. Use of investigational agents within 5 terminal elimination half-lives prior to the transplantation 2. Malignancy within 5 years prior to transplantation 3. Positive serology for human immunodeficiency virus (HIV) 4. Clinically relevant active infection(s) as judged by the investigator 5. Contemporaneous participation in medical device studies 6. Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities 7. Inability by the judgement of the investigator to participate in the trial for any other reason Exclusion criteria for IMLIFIDASE patients 1. Previous treatment with imlifidase 2. Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment 3. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test 4. Breast feeding or pregnancy 5. Hypersensitivity to the active substance (imlifidase) or to any of the excipients 6. Ongoing serious infections 7. Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP 8. 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 9. 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: 1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; (i) oral, (ii) intravaginal, or (iii) transdermal 2. progestogen-only hormonal contraception associated with inhibition of ovulation; (i) oral, (ii) injectable, or (iii) implantable 3. intrauterine device (IUD) 4. intrauterine hormone-releasing system (IUS) 5. bilateral tubal occlusion 6. vasectomised partner 7. true abstinence: When this is in line with the preferred and usual lifestyle of the patient. \[Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\] 10. Any other reason that, in the view of the investigator, precludes transplantation Exclusion criteria for patients in the NON-COMPARATIVE HISTORICAL REFERENCE COHORT 1. Patients treated with mammalian target of rapamycin (mTOR) inhibitors 2. Patients treated with belatacept

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is an open-label, non-randomised trial in highly sensitized adult kidney transplant patients with positive XM against an available deceased donor.\n\nThe rational for a non-randomised trial is that no other effective or approved desensitization protocol exists in deceased-donor kidney transplantation that would provide a suitable control.\n\nA non-comparative concurrent reference cohort from participating sites will be included to address differences in-site practice and experience.\n\nA non-comparative historical reference cohort from the CTS registry will be included to address the outcome in a less sensitized patient group.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 225, 'type': 'ESTIMATED'}}

2024-05-01