EIGHT TREG for End-stage renal disease (chronic renal failure) requiring kidney transplantation

Inclusion criteria

• {"criterion_text":"- Man or woman with chronic renal failure requiring kidney transplantation and approved to receive a primary kidney allograft from a living donor.\n- Affiliated or beneficiary of a social security scheme\n- Speaking and understanding French\n- Weight between 50 and 100 kg\n- Up-to-date vaccination against SARS Cov2 depending on the health situation and the rules in force with last recall done at least 6 to 1 month prior to visit 1\n- Negative microlymphocytotoxicity (LCT) and flow cytometry crossmatches regardless of HLA compatibility\n- Signed and dated written informed consent\n- Aged at least of 18 years the day the consent is signed\n- Able to commence the IS regimen at the protocol-specified time point\n- As a precautionary measure, women of childbearing age should use an effective method of birth control, and male participants should use contraception to avoid partner pregnancy for the duration of the trial."}

Exclusion criteria

• {"criterion_text":"- Patient has previously received any tissue or organ transplant other than the planned kidney graft\n- Patients unable to freely give their informed consent (e.g. patients under guardianship, curatorship, protection of justice).\n- Patients deprived of their liberty.\n- Genetically identical to the prospective organ donor at the HLA loci\n- Known contraindication to the protocol-specified treatments / medications or components used in the manufacture of the experimental drug\n- Previous treatment with any desensitisation procedure (with or without IVIg)\n- Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal / squamous cell carcinoma of the skin).\n- Evidence of significant local or systemic infection on visit 1\n- Malignant or pre-malignant haematological conditions\n- Ongoing treatment with systemic IS drugs at visit 1 (except corticoids < 10 mg).\n- 4.\tPanel Reactive Antibodies (PRA) or “Taux de Greffons Incompatibles” (TGI) grade > 0 within 6 months prior to enrolment.\n- Any vaccine (or vaccine recall) dated within 3 months on visit 1 except the SARS Cov2\n- Participation in another clinical trial during the study or within 28 days prior to the planned study entry and / or exposure to an investigational product during the study or within 28 days prior to the planned study entry (date of signature of the consent collection form).\n- Women who are pregnant (or planning to be during the course of the study) or breastfeeding or women with a positive pregnancy test on enrolment (visit 1, screening failure).\n- Psychological, familial, sociological or geographical factors that potentially hampering compliance with the study protocol and follow-up visit schedule\n- Any form of drug abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may invalidate communication with the investigator and/or designated study personnel\n- Any pro-coagulant disposition, as evidences by a past history of thromboembolic disease or abnormal laboratory coagulation parameters which, in the judgement of the investigator, would place the subject at undue risk\n- Any condition resulting in a substantial reduction in the volume of the pulmonary vasculature or an increase in the pulmonary vascular resistance. Any disease or disease process leading to substantially elevated pulmonary arterial pressure (as evidences by electrocardiography, echocardiography, radiology or cardiac catheterization) or right heart hypertrophy or dysfunction.\n- Known atrial or ventricular septal defects posing a risk of paradoxical embolism of infused cells or cell aggregates."}

Primary endpoints

• {"endpoint_text":"- Occurrence of a dose-limiting toxicity up to visit 10, at 3 months post-graft. A Dose-Limiting Toxicity (DLT) is defined as a clinically significant AE or abnormal laboratory value: \tUnrelated to the kidney transplant, intercurrent illness, or concomitant medications  Grade 3, 4 or 5 non-hematologic toxicity (with exceptions)","definition_or_measurement_approach":"Dose-Limiting Toxicity (DLT) defined as a clinically significant adverse event or abnormal laboratory value that is unrelated to the kidney transplant, intercurrent illness, or concomitant medications and is Grade 3, 4 or 5 non-hematologic toxicity (with exceptions). Occurrence assessed up to visit 10 (3 months post-graft)."}

Secondary endpoints

• {"endpoint_text":"- Occurrence of a DLT up to 6- and 12-months post-graft, and anatomopathological and im-munohistological (HD) analysis of the graft biopsies at 1- and 3-months post-graft.","definition_or_measurement_approach":"DLT occurrence assessed up to 6 and 12 months post-graft; graft biopsies undergo anatomopathological and immunohistological analyses at 1 and 3 months post-graft."}
• {"endpoint_text":"- Incidence, duration and severity of infections, and total immunosuppressive burden at one-year post-graft.","definition_or_measurement_approach":"Incidence, duration and severity of infections recorded; total immunosuppressive burden measured at one-year post-graft (comparison to historical data)."}
• {"endpoint_text":"- 3\tReal time follow-up of blood cell count, analysis of the DSA and of cytokines in plasma and urine; kinetic of absolute count of blood cells and high density spectral immunophenotyping at protein and transcriptional levels of PBMC; tracking the infused cells in blood; identifying Tregs clones emerging; evaluating the suppressive capacity of circulating Tregs; evaluating the reac-tivity of circulating T cells ; immunohistochemical staining and spatial transcriptomic of graft biopsies","definition_or_measurement_approach":"Real-time blood cell counts; analysis of donor-specific antibodies (DSA) and cytokines in plasma and urine; kinetics of absolute blood cell counts; high-density spectral immunophenotyping of PBMC at protein and transcriptional levels; tracking infused cells in blood; identification of emerging Treg clones; assessment of suppressive capacity and reactivity of circulating T cells; immunohistochemical staining and spatial transcriptomics of graft biopsies."}
• {"endpoint_text":"- 4\tComparison of blood Tregs profile, emerging clones, and donor reactive T cells; and perturba-tion of graft infiltrate after cell therapy compared to standard treatment from a control biocollec-tion (DIVAT declared on 09/05/2011 under the n°DC-2011-1399) and historical databases.","definition_or_measurement_approach":"Comparative analysis of blood Treg profiles, emerging clones, donor-reactive T cells, and graft infiltrate perturbation after cell therapy versus standard treatment using control biocollection (DIVAT) and historical databases."}

France

Earliest CTIS Part Ii Submission Date

25-11-2024

Latest Decision Or Authorization Date

20-12-2024

Processing Time Days

25

Number Of Sites

1

Number Of Participants

9

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nantes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France