Desensitization Using Clazakizumab? (anti-il-6) in Highly-hla Sensitized Patients Awaiting Kidney Transplant (nct03380962)

Purpose: IL-6 mediates inflammation and activation of T-cells, B-cells & plasma cells. Thus, IL-6 may represent an important target for desensitization (DES). Here we report a 12M follow-up of this single center Phase I/II study to assess safety & efficacy of Clazakizumab (anti-IL-6, Vitaeris) for DES in highly-HLA sensitized (HS) patients. Methods: Ten HS patients (cPRA >50%) received PLEX x5 followed by IVIg 2gm/kg X1. Post-IVIg, patients received anti-IL-6 25mg SC Q4W X6 with monitoring of HLA antibody and other immune parameters. Study end point was transplantation by day 270 post-Rx. Transplanted patients received anti-IL6 25mg SC Q4W. After protocol biopsy at 6M, patients continued anti-IL6 for 12M post-transplant. The primary end point was safety and ability to modify HLA antibodies from baseline. All transplanted patients received induction with alemtuzumab and maintained on tac/mmf/pred. Results: Nine patients were transplanted. Briefly, mean time from dialysis to transplant was 96±52M and from last claza to transplant was 5.5±3.6M. All patients had previous transplants; 78% had cPRA 99-100%, 67% were B-cell FCMX+ and CII DSA+ @transplant. Mean MFI for HLA CI & CII were: pre-des v. post claza: CI 13062±3123 v. 8585±4597 (p=0.05) and CII 13519±2966 v. 8344±4836 (p=0.03). Figure 1 showed DSA MFI pre & post-tx to month 12. No patients had detectable DSA @6M post-tx. Protocol biopsies @6M in 8 patients (89%) showed mean g+ptc: 0.75±1.9, cg: 0.375±0.99, c4d: 0.625±1.1, ci+ct: 1.25±1.4, and i-IFTA: 0.75±1.1 respectively (Figure2). Two patients developed rejection CMR/ABMR and cABMR as a result of DSA rebound. Mean eGFR @12M was 51±26 ml/min. Conclusions: Overall, there was a significant reduction in HLA MFI for CI and CII post-claza in 9/10 patients. No patient had detectable DSA 6M post-transplant. Therefore, anti-IL-6 appears promising as a desensitization agent when used with PLEX + IVIg. Anti-IL-6 also reduced antibody rebound post-PLEX + IVIg likely allowing successful HLAi transplantation for these patients. An increase in Treg (CD4+,CD25+,FoxP3+, CD127low) was seen in claza treated patients post-transplant.Vitaeris, Inc.