MedDRA version: 20.0 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Sponsors
Hansa Biopharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
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. End-stage renal disease (ESRD) active on the renal transplant waiting list of a kidney allocation system at the time of screening 2. High sensitisation with the highest unmet medical need unlikely to be transplanted under the available kidney allocation system including prioritisation programmes for highly sensitised patients (see table below for recommended reference thresholds. Note: highest unmet medical need is per investigator's discretion) 3. Known DSA against an available deceased donor 4. Positive crossmatch test determined by Complement-Dependent Cytotoxicity crossmatch (CDCXM) and/or Flow Cytometry Crossmatch (FCXM) against an available deceased donor. If physical crossmatch tests are not practically possible due to lack of time, patients may be included on a Virtual Crossmatch (vXM) predictive of a positive crossmatch test. 5. Signed Informed Consent obtained before any trial-related procedures 6. Willingness and ability to comply with the protocol Recommended reference thresholds for highest unmet medical need depending on sensitisation within different European allocation system (see 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 Willingness and ability to comply with the protocol Inclusion Criteria for patients in the non-comparative historical reference cohort 1. End-stage renal disease with a kidney transplant from a deceased donor 2. Being transplanted in Europe after 01-Jan-2010 and included in the CTS registry 3. PRA = 50% (CDC T or B cell PRA, cPRA, or virtual PRA [vPRA]) 4. Maintenance immunosuppression (intention to treat) with calcineurin inhibitor, mycophenolate mofetil (MMF) and corticosteroids in combination Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 125 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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) (including hepatitis B [HBV], hepatitis C [HCV], cytomegalovirus [CMV], Epstein Barr Virus [EBV], tuberculosis) 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. Suspicion of Covid-19 infection or positive SARS-CoV-2 test 4. Breast feeding or pregnancy 5. Hypersensitivity to the active substance (imlifidase) or to any of the excipients (see section 5.1) 6. Ongoing serious infections (including HBV, HCV, CMV, EBV, tuberculosis) 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. 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 mTOR (mammalian target of rapamycin) inhibitors 2. Patients treated with belatacept
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the 1-year graft failure-free survival in highly sensitised kidney transplant patients, pre-treated with imlifidase to turn a positive crossmatch against a deceased donor negative;Secondary Objective: Secondary objectives relating to imlifidase treatment group •renal function up to 1 year after transplantation •patient survival 1 year after transplantation •graft survival 1 year after transplantation •crossmatch conversion within 24 hours of imlifidase treatment •HLA/DSA antibody levels up to 1 year after transplantation •pharmacokinetic (PK) profile of imlifidase •pharmacodynamic (PD) profile of imlifidase •immunogenicity profile of imlifidase (anti-drug antibodies [ADAs]) •delayed graft function (DGF) •for further secondary objectives relating to imlifidase treatment group see protocol Secondary Objectives relating to the non-comparative concurrent reference cohort (see protocol) Secondary Objectives relating to the randomly selected non-comparative historical reference cohort retrieved from the CTS registry (see protocol) Exploratory objective relating to the imlifidase treatment group and the concurrent reference cohort (see protocol);Primary end point(s): 1-year graft failure-free survival rate in patients who have been kidney transplanted after imlifidase treatment. ;Timepoint(s) of evaluation of this end point: One year after transplantation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints relating to imlifidase treatment - Renal function at several time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed by estimated glomerular filtration rate (eGFR) and serum/plasma creatinine levels - Patient survival at 1 year after transplantation - Graft survival at 1 year after transplantation - Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after imlifidase treatment - HLA/DSA antibody levels at several time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment - Imlifidase PK up to 14 days after imlifidase treatment - Imlifidase PD up to 9 days after imlifidase treatment - ADAs up to 1 year after imlifidase treatment - Frequency of DGF - Proportion of patients with biopsy- and serology (DSA)-confirmed AMRs over 1 year - Proportion of patients with biopsy confirmed CMRs over 1 year. - Safety over 1 year as measured by reported SAEs - Safety assessed as proportion of patients with infusion-related reactions within 48 hours of imlifidase infusion - Safety assessed as proportion of patients with severe or serious infections within 30 days after transplantation - Change in patient-reported life participation, as measured by the PROMIS Social Health domain “Ability to participate in social roles & activities, PROMIS-SF-8a”, from baseline to 1 year after transplantation Secondary endpoints relating to the non-comparative concurrent reference cohort - Graft failure-free survival at 1 year after transplantation - Renal function at 1, 3 and 6 months and 1 year after transplantation as assessed by eGFR and serum/plasma creatinine levels - Patient survival at 1 year after transplantation - Graft survival at 1 year after transplantation - Frequency of DGF - Proportion of patients with biopsy- and serology (DSA)-confirmed AMRs over 1 year - Proportion of patients with bi | — |
Countries
Austria, Belgium, Czechia, Czech Republic, France, Germany, Italy, Netherlands, Slovenia, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical contact information
Hansa Biopharma AB
Outcome results
None listed