A Single-arm, Multi-centre Trial to Evaluate Efficacy and Safety of Imlifidase in Highly Sensitised Children (1-17 Years) Receiving a Kidney Transplant With Positive Crossmatch Against a Living or Deceased Donor Converted to Negative After Imlifidase Treatment

20-HMedIdes-21

The goal of this clinical trial is to learn about the efficacy and safety of imlifidase in highly sensitized paediatric patients, 1-17 years old, with end stage renal disease (ESRD). The main questions it aims to answer are: * Does imlifidase treatment result in crossmatch conversion that enables transplantation? * How is the function of the transplanted kidney? The participants will be hospitalised in accordance with the normal routines for transplanted patients. The patients will receive medication to prevent rejection of the donor kidney, and because such treatment make the body more vulnerable medications to prevent infections.

2023-06-02

2024-09-30

2029-09-30

Recruiting

Early phase I

10

Inclusion Criteria: 1. Signed Informed Consent obtained from patient/parent/legal guardian/independent witness (depending on patient's age) before any trial-related procedures 2. Highly sensitised patient with panel reactive antibodies (PRA) ≥80% 3. Male or female patient between the age of 1 to 17 years (up to the day before the 18th birthday) at the time of screening 4. Patient with end-stage renal disease (ESRD) and waiting for a renal transplant from a living or deceased donor 5. Patient must be transplantable (including size mismatch) at the time of obtaining informed consent for trial participation 6. Patients who have previously undergone desensitisation unsuccessfully with plasmapheresis/IVIg/anti-CD20 or have an anti-HLA antibody status deemed too difficult to make a successful desensitisation (judgement based on physicians' previous experience with similar patients) 7. Positive crossmatch (XM) test determined by flow cytometry crossmatch (FCXM) and/or complement-dependent cytotoxicity crossmatch (CDCXM) tests against the donor. For the DD patients, 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. 8. Willingness and ability to comply with the protocol as judged by the investigator Exclusion Criteria: 1. Previous treatment with imlifidase 2. IVIg treatment within 28 days prior to imlifidase treatment 3. Desensitisation treatment(s) within 1 month prior to the current transplantation 4. Hypersensitivity to the active substance (imlifidase) or to any of the excipients and to other immunosuppressive drugs specified in the protocol 5. Ongoing serious infections 6. Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP 7. At the time of transplantation: severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease, active peripheral vascular disease, proven hypercoagulable conditions/events or oxygen dependent respiratory disease 8. Malignancy within 3 years prior to transplantation 9. ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients) 10. Any other reason that, in the view of the investigator, precludes transplantation 11. Breast feeding or pregnancy, if applicable 12. Woman of fertile age and sexually active without adequate contraceptive measures to avoid pregnancy during the interventional trial period (i.e. up to 6 months after transplantation) 13. Suspicion of Covid-19 infection or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test 14. Positive serology for human immunodeficiency virus (HIV) 15. Clinical signs of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), or Epstein Barr virus (EBV) infection 16. Donor with positive serology for HIV, HBV, HCV, CMV or EBV to a patient with negative serology (mismatch serology) 17. Clinically relevant active infection(s) as judged by the investigator 18. Tuberculosis 19. Use of other investigational agents within 5 terminal elimination half-lives prior to the transplantation 20. Contemporaneous participation in medical device studies 21. Known mental incapacity or language barriers precluding patients'/parents'/legal guardians' adequate understanding of the informed consent information and the trial activities 22. Inability by the judgement of the investigator to participate in the trial for any other reason

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': "This is an open-label, non-randomised trial in highly sensitized paediatric kidney transplant patients with positive XM against an available DD or LD.\n\nThe rationale for a non-randomised trial in DD kidney transplantation is that there are no other effective or approved desensitisation protocols that would provide a suitable or ethical control.\n\nThe rationale for a non-randomised trial in LD kidney transplantation is that potential control treatments have already been tried unsuccessfully in the patients or such treatments are judged as highly unlikely to succeed based on the breadth and depth of the patients' sensitisation. Treatment with little anticipation of success would expose the patients to unnecessary immunosuppression.", 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ESTIMATED'}}

2023-11-02