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 all-cause 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/1.73 m 2 (−10.2, −5.8) vs −5.2 mL/min/1.73 m 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.