Induction of Immune Tolerance in Living Related HLA-Matched Kidney Transplantation: A Phase 3 Randomized Clinical Trial

This Phase 3 multi-center, randomized, controlled clinical trial evaluated investigational cellular product (MDR-101) to produce immune tolerance vs standard of care, in kidney transplant recipients. Adult recipients of kidneys from 2-haplotype HLA-matched living siblings were randomized 2:1 to Treatment (n=20) or Control (n=10). The MDR-101 product was from the same kidney donor. Treatment recipients received a non-myeloablative conditioning protocol with rabbit antithymocyte globulin and low-dose total lymphoid irradiation (10 fractions). MDR-101 was infused (D11). Steroids were withdrawn by D10 and mycophenolate by D39. Tacrolimus was continued until D180 and tapered to withdrawal 1-year post-transplant if donor hematopoietic mixed chimerism was ≥5%. Controls received immunosuppression per institutional standard of care. Twenty recipients received the MDR-101 infusion, none developed GVHD. Nineteen (95%) successfully discontinued all immunosuppression approximately 1-year post-kidney transplant. Fifteen (75%) reached the primary study end-point of immunosuppression-free for > 2 years. Four resumed immunosuppression: One with recurrent IgA nephropathy (IgAN) one with recurrent IgAN and rejection; one with rejection; one with borderline biopsy changes. Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than two years with no death, graft loss, DSA or GVHD and demonstrated improved quality of life compared to standard treatment. Clinical Trial Registration - NCT03363945 (not part of word count)