IMLIFIDASE IN LIVING DONOR RENAL TRANSPLANTATION: HIGHLY SENSITIZED RECIPIENTS
- Conditions
- kidney trasplant
- Registration Number
- 2024-513607-14-00
- Lead Sponsor
- Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer
- Brief Summary
To evaluate the ability of Imlifidase treatment to achieve a negative virtual crossmatch in patients with available live donor kidney
- Detailed Description
The patients between 18 and 65 years will be flow cytometry crossmatch (FC-XM) positive against an available living donor. The imlifidase treatment will turn the crossmatch test negative prior to transplantation. A second dose of imlifidase can be given within 24 hours if the first dose is considered not to have sufficient effect. If a second dose is given, a confirmatory FCXM test will be performed pre-second imlifidase dosing and between 2-6 hours following the second dose.
Recruitment & Eligibility
- Status
- Ended
- Sex
- Not specified
- Target Recruitment
- 10
•Highly sensitized (cPRA ≥ 50%) kidney transplant candidates between 18 and 65 years.
• Low probability to get a transplant in a kidney exchange program (KEP) from a living donor.
• Included in the living donor program, with an accepted potential living donor.
• Donor and recipient must meet the eligibility criteria for donation and kidney transplantation respectively at the Hospital Clinic of Barcelona and the national guidelines.
• Presence of donor-specific antibody/crossmatch positive (DSA/FC-XM+) non-HLA identical donor. o at least one DSA with MFI >3.000. o and DSA MFI <10.000 (in serum samples diluted 1/64). o and maximum two Class II DSAs. o and maximum 17 points in Jordan RIS Score (DSA 2500-5000: 2 points; DSA MFI 5001-10000: 5 points; DSA MFI > 10000: 10 points)
• Women of childbearing age must take contraceptive measures because imlifidase is not recommended during pregnancy.
• Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
Known contraindications for therapy with IVIG, Rituximab, plasma exchange (PLEX) or imlifidase.
Subjects with active CMV or EBV infection as defined by positive PCR.
Subjects with a known history of previous myocardial infarction within one year of screening.
Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease.
Patients with a kidney disease with high risk of recurrence and/or complement-associated kidney disease (aHUS, etc).
Subjects with Protein C and Protein S deficiency.
Pregnant and lactating women
Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP.
Known allergy to Imlifidase or excipient of the drug preparation
Recipients of Deceased Donors (DBD, Extended Criteria Donors (ECD) or DCD).
A positive Complement-Dependent Cytotoxicity (CDC) Crossmatch against the living donor.
HIV-positive subjects.
Subjects who test positive for HBV infection [positive HBVsAg or HBVeAg/DNA] or HCV infection [RNA+].
Subjects with active TB.
Subjects with selective IgA deficiency, those who have known anti-IgA antibodies, and those with a history of anaphylaxis or severe systemic responses to any part of the clinical trial material.
Subjects who have received or for whom multiple organ transplants are planned.
A significantly abnormal general serum screening lab result defined as WBC<3.0x103/ml, Hgb<8.0 g/dL, platelet count <100x103/ml, SGOT>3xupper limit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of patients with conversion of a positive virtual crossmatch to negative within 6 hours after imlifidase treatment (up to two doses). Proportion of patients with conversion of a positive virtual crossmatch to negative within 6 hours after imlifidase treatment (up to two doses).
- Secondary Outcome Measures
Name Time Method To evaluate flow cytometry T-cell crossmatch conversion within 24 hours of imlifidase treatment, requirement of a second dose of imlifidase. To evaluate flow cytometry T-cell crossmatch conversion within 24 hours of imlifidase treatment, requirement of a second dose of imlifidase.
To evaluate the rebound of preexisting donor specific antibodies (DSA) (difference between MFI of each DSA daily - until D+14 - compared to pre-imlifidase administration) To evaluate the rebound of preexisting donor specific antibodies (DSA) (difference between MFI of each DSA daily - until D+14 - compared to pre-imlifidase administration)
To evaluate the appearance of de novo DSAs (any DSA no present in pre-transplant or historical) daily - until D+14. To be considered positive the bead MFI should be over 750 and to be above the bead specific threshold related to the lowest bead of the same locus. To evaluate the appearance of de novo DSAs (any DSA no present in pre-transplant or historical) daily - until D+14. To be considered positive the bead MFI should be over 750 and to be above the bead specific threshold related to the lowest bead of the same locus.
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 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
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 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
To evaluate patient survival 1 year after transplantation To evaluate patient survival 1 year after transplantation
To evaluate the graft survival at 12 months (both overall and death-censored analysis) To evaluate the graft survival at 12 months (both overall and death-censored analysis)
To evaluate the incidence of acute allograft rejection within 12 months (overall and stratified by type: cell mediated rejection or antibody-mediated rejection) To evaluate the incidence of acute allograft rejection within 12 months (overall and stratified by type: cell mediated rejection or antibody-mediated rejection)
To evaluate safety of Imlifidase treatment with regards to infusion related reactions occurring within 48 hours of Imlifidase infusion To evaluate safety of Imlifidase treatment with regards to infusion related reactions occurring within 48 hours of Imlifidase infusion
To evaluate the adverse events within 30 days after transplantation To evaluate the adverse events within 30 days after transplantation
To evaluate to severe or serious infections (that required hospitalization) within 30 days after transplantion, at 6 and 12 months To evaluate to severe or serious infections (that required hospitalization) within 30 days after transplantion, at 6 and 12 months
To evaluate safety of Imlifidase treatment with regards to reported serious adverse events (SAEs) To evaluate safety of Imlifidase treatment with regards to reported serious adverse events (SAEs)
Trial Locations
- Locations (1)
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Hospital Clinic De Barcelona🇪🇸Barcelona, SpainFritz DiekmannSite contact+932275400fdiekman@clinic.cat