The ProTreg21 Protocol: Phase I/IIa Regulatory T cell Therapy Clinical Trial in Deceased-Donor Kidney Transplantation.

BACKGROUND: Long-term maintenance immunosuppression post kidney transplantation is associated with infection, malignancy, cardiovascular morbidity, and chronic nephrotoxicity. Adoptive autologous regulatory T-cell therapy may permit safer immunosuppression minimisation, but experience in deceased kidney transplantation remains limited. METHODS: ProTreg21 is a single-centre, open-label, controlled phase I/IIa trial using a 3+3 single-ascending-dose design. Eligible adults aged 18-70 years undergoing primary deceased- donor kidney transplantation will receive low-dose rabbit anti-thymocyte globulin (Thymoglobulin; 1.5 mg/kg on days 0 and 1) and standard of care immunosuppression. In addition, participants in the investigational arm will receive a single infusion of ex-vivo expanded autologous polyclonal regulatory T cells (Treg02) at ascending doses of 0.5 × 106, 1 × 106, 3 × 106 cells/kg on day 16 (±2 days). The primary objective is to evaluate safety and tolerability; the primary endpoint is a protocol-defined Treg02 related defined dose-limiting toxicity within 14 days after infusion. Feasibility and longer-term safety will be secondary outcomes, whereas biopsy proven acute rejection, graft function, infection, malignancy, immunosuppression reduction, and immune biomarkers through week 60 will be exploratory outcomes. RESULTS: Here we describe the approved trial protocol; no trial results are reported. CONCLUSIONS: ProTreg21 will establish whether Treg02 can be manufactured and administered safely following deceased donor kidney transplantation and will provide exploratory data to inform subsequent efficacy trials.