Clazakizumab in the treatment of chronic active antibody-mediated kidney transplant rejection: Results from the IMAGINE phase 3, randomized, double-blind, placebo-controlled study

Chronic active antibody-mediated rejection (caAMR) is a leading cause of kidney allograft loss; there are no approved therapies.Clazakizumab binds IL-6 and was associated with reduced donor-specific antibodies and stabilized eGFR in kidney transplant (KTx) recipients with caAMR in a phase 2 study.We report the final analysis from the phase 3 IMAGINE trial, the largest placebo-controlled study in KTx recipients with caAMR.KTx recipients were randomized 1:1 to clazakizumab (12.5 mg SC Q4W) or placebo.One-year interim analysis of eGFR (N=115) indicated that the trial was unlikely to meet the primary outcome (time to allcause allograft loss or irreversible loss of allograft function), resulting in early termination.In the final analysis (N=191), least-squares mean eGFR change from baseline to Week 52 (95% CI) for clazakizumab was -8.0 mL/min/1.73m 2 (-10.2,-5.8) vs -5.2 mL/min/1.73m 2 (-7.4,-3.1) for placebo (p=0.959).Allograft loss or irreversible loss of allograft function was experienced by 28.3% and 22.2% of patients treated with clazakizumab and placebo, respectively.Reduced CRP was observed with treatment.No safety concerns were noted.In conclusion, IL-6 blockade with clazakizumab did not translate into improvement in eGFR in KTx recipients with caAMR.