everolimus for Kidney transplantation|NK-mediated kidney graft rejection

Inclusion criteria

• {"criterion_text":"- Major renal transplant patient"}
• {"criterion_text":"- Patient who had a renal graft biopsy as part of the usual follow-up finding microvascular inflammatory lesions (glomerulitis + peritubular capillaritis ≥ 2) associated with moderate chronic lesions (cg < 3 and cv < 3) according to the Banff classification 2013"}
• {"criterion_text":"- Having a predictable “missing self”: patient having a mismatch between the HLA class I ligands of inhibitory KIRs present in the recipient and the ligands present in the recipient"}
• {"criterion_text":"- Patient receiving at least dual immunosuppressive therapy including: an anticalcineurin (tacrolimus or cyclosporine), an antimetabolite (mycophenolic acid (CELLCEPT or MYFORTIC) or azathioprine (IMUREL))."}
• {"criterion_text":"- Taking effective contraception for up to 8 weeks after the end of treatment with everolimus (CERTICAN)"}
• {"criterion_text":"- Patient affiliated to a social insurance regimen"}
• {"criterion_text":"- An absence of anti-endothelial cell antibodies in their serum tested for by an endothelial cross match"}
• {"criterion_text":"- At least 1 confirmed missing self: the recipient has at least one functional KIR inhibitor present genotypically whose HLA class I ligand is not present in the donor"}

Exclusion criteria

• {"criterion_text":"- Patients at high immunological risk: presence of preformed specific anti-HLA antibodies or hyperimmunized patients (incompatible graft rate > 85%) on the day of the transplant."}
• {"criterion_text":"- Subject participating in another research including an exclusion period still in progress at pre-inclusion"}
• {"criterion_text":"- Pregnant, breastfeeding women, minors, adults under guardianship or curatorship"}
• {"criterion_text":"- Proteinuria > 1 g/day (or 100 mg/mmol creatininuria)"}
• {"criterion_text":"- History of poor tolerance of everolimus"}
• {"criterion_text":"- Hypersensitivity to everolimus, sirolimus or one of its excipients as mentioned in the SPC of everolimus paragraph 4.3 and 6.1."}
• {"criterion_text":"- Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome"}
• {"criterion_text":"- Surgery planned for the next 6 months"}
• {"criterion_text":"- Severe chronic lesions (cg > 2 or cv > 2) according to the Banff 2013 classification on the classic histological examination of a graft biopsy"}
• {"criterion_text":"- Presence of donor-specific anti-HLA antibodies in their serum on the day of the biopsy searched by Luminex"}
• {"criterion_text":"- Positive endothelial cross match with serum from the day of the biopsy"}

Primary endpoints

• {"endpoint_text":"- Relative variation in Glomerular Filtration Rate (GFR) estimated by the CKD-EPI method between D-15 and M6 after starting everolimus.","definition_or_measurement_approach":"GFR estimated by the CKD-EPI method measured at baseline (D-15) and at 6 months (M6) after starting everolimus; relative change between these timepoints."}

Secondary endpoints

• {"endpoint_text":"- Histological: variation in the microvascular inflammation score (g+cpt) and chronic glomerular (cg) and vascular (cv) lesions determined according to the Banff 2013 classification between D-15 and M6","definition_or_measurement_approach":"Histological scoring (g+cpt, cg, cv) on graft biopsy specimens evaluated per Banff 2013 classification between baseline (D-15) and month 6."}
• {"endpoint_text":"- Biological: variation in the degree of in vitro activability of NK between D0 and M6","definition_or_measurement_approach":"In vitro assays measuring NK cell activability at baseline (D0) and at month 6 to assess change in NK activability."}
• {"endpoint_text":"- Clinical: relative variation in the proteinuria/creatininuria ratio between D-15 and M6","definition_or_measurement_approach":"Measurement of proteinuria/creatininuria ratio at baseline (D-15) and at month 6; assessment of relative change."}

France

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

5

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Hospices Civils De Lyon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France