BELATACEPT for Kidney transplantation | Subclinical antibody-mediated rejection | De novo donor-specific antibodies (dnDSA)

Inclusion criteria

• {"criterion_text":"- Kidney transplant recipient\n- Adult\n- De novo DSA (MFI > 1000 using the Luminex single antigen beads assay or positive with the manufacturer criteria according to the Luminex assay) absent on the day of kidney transplantation and in the sera prior to kidney transplantation\n- No clinical graft dysfunction at time of DSA detection (< 20 % variation of eGFR compared to last 3 months before detection and < 0,5 g/g proteinuria/creatinuria ratio)\n- Randomization inclusion criteria: - Patients with active sABMR, according Banff 2019 classification, with very slight transplant glomerulogathy (cg = 0 or 1)."}

Exclusion criteria

• {"criterion_text":"- Specific treatment for DSA occurrence before kidney graft biopsy: IVIG or rituximab or plasmapheresis or immunoabsorption\n- ABO incompatible kidney transplantation\n- Combined transplantation\n- Randomization exclusion criteria: \tNo sABMR or chronic active sABMR (cg > 1) on biopsy \tContraindication to Tacrolimus marketed as capsule or tablet pharmaceutical form o\tHypersensitivity to tacrolimus or other macrolides o\tHypersensitivity to any of the excipients \tContraindication to NULOJIX 250 mg powder for concentrate for solution for infusion: o\tTransplant recipients who are Epstein-Barr virus (EBV) seronegative or serostatus unknown. o\tHypersensitivity to the active substance or to any of the excipients \tHistory of severe opportunistic infection before randomization \tHistory of infection with HBV, HCV or HIV \tEBV negative serology \tHistory of post-transplant lymphoproliferative disorder."}

Primary endpoints

• {"endpoint_text":"- Proportion in each arm, at 12 months post-V0 (Biopsy), of patients with: - decrease eGFR > 20% at 12 months post-V0 (Biopsy), according to CKD-EPI formula - or bad features on 12-month protocol biopsy: cg > 1 - or chronic active ABMR according Banff 2019 classification, - or < 50 % MFI reduction of DSA, - or proteinuria/creatinuria ratio > 0.5 g/g, - or death, - or graft loss.","definition_or_measurement_approach":"Measured at 12 months post-V0 (Biopsy): decrease in eGFR >20% using CKD-EPI formula; presence of bad features on 12-month protocol biopsy (cg>1); diagnosis of chronic active ABMR per Banff 2019 classification; <50% reduction in MFI of DSA measured by Luminex single antigen assay; proteinuria/creatinuria ratio >0.5 g/g; occurrence of death; graft loss."}

Secondary endpoints

• {"endpoint_text":"- To compare in both randomized arms: 1)\tAll Banff 2019 elementary lesions of the kidney graft biopsy performed at 12 months after post-V0 (Biopsy)","definition_or_measurement_approach":"Assessment of Banff 2019 elementary lesion scores on 12-month graft biopsy."}
• {"endpoint_text":"- 2)\tSerum creatinine and calculation of eGFR according to CKD-EPI formula at 12 and 36 months post-V0 (Biopsy)","definition_or_measurement_approach":"Serum creatinine measured and eGFR calculated using CKD-EPI at 12 and 36 months post-V0."}
• {"endpoint_text":"- 3)\tProteinuria/creatininuria ratio at 12 and 36 months post-V0 (Biopsy)","definition_or_measurement_approach":"Proteinuria/creatininuria ratio measured at 12 and 36 months post-V0."}
• {"endpoint_text":"- 4)\tBad features on 12-month biopsy (cg>1)","definition_or_measurement_approach":"Presence of cg>1 on 12-month protocol biopsy per Banff criteria."}
• {"endpoint_text":"- 5)\tBiopsy proven acute T cell rejection rate according to Banff 2019 classification","definition_or_measurement_approach":"Rate of biopsy-proven acute T cell–mediated rejection classified per Banff 2019."}
• {"endpoint_text":"- 6)\tMFI of the DSA at 12 months post randomization with a Luminex single antigen assay and at 36 months post-randomization from medical charts","definition_or_measurement_approach":"Mean fluorescence intensity (MFI) of DSA measured by Luminex single antigen assay at 12 and 36 months post-randomization."}
• {"endpoint_text":"- 7)\tAdverse events’ collect (Occurrence of BK virus, CMV and EBV’s viremia, cardiovascular events, hospitalizations)","definition_or_measurement_approach":"Collection of adverse events including BK/CMV/EBV viremia, cardiovascular events, and hospitalizations from medical records."}
• {"endpoint_text":"- 8)\tGraft loss and death at 12 and 36 months post-V0 (Biopsy) from medical charts","definition_or_measurement_approach":"Graft loss and death recorded at 12 and 36 months from medical charts."}
• {"endpoint_text":"- To compare the groups formed at the initial biopsy with respect to: 9)\tSerum creatinine and calculation of eGFR according CKD-EPI formula, and proteinuria/creatininuria ratio at 12 and 36 months","definition_or_measurement_approach":"Serum creatinine, eGFR (CKD-EPI) and proteinuria/creatinuria ratio at 12 and 36 months compared between biopsy-formed groups."}
• {"endpoint_text":"- 10)\tGraft loss and death at 12 and 36 months from medical charts","definition_or_measurement_approach":"Graft loss and death outcomes at 12 and 36 months collected from medical charts."}
• {"endpoint_text":"- 11)\tNumber of patients with sABMR according to Banff 2019 classification on biopsy performed at 12 months as part of routine care or before in the group without sABMR on initial biopsy divided by the time between initial biopsy and the first biopsy showing sABMR","definition_or_measurement_approach":"Count of patients with sABMR per Banff 2019 on 12-month (or earlier) biopsy divided by time from initial biopsy to first sABMR biopsy."}

France

Earliest CTIS Part Ii Submission Date

06-05-2025

Latest Decision Or Authorization Date

24-06-2025

Processing Time Days

49

Number Of Sites

17

Number Of Participants

290

Primary sponsor

Full Name

Centre Hospitalier Universitaire Rouen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France