Clazakizumab in the Treatment of Chronic Active Antibody-Mediated Kidney Transplant Rejection: Results from the IMAGINE Phase 3 Randomized, Double-Blind, Placebo-Controlled Study
In the phase 3 IMAGINE trial, the anti–IL-6 antibody clazakizumab did not meet its primary efficacy endpoint for chronic active antibody-mediated rejection (caAMR) in kidney transplant recipients, and the trial was stopped for futility at interim analysis.
Background
Chronic active antibody-mediated rejection is a leading cause of late kidney allograft loss, and no drug is approved to treat it. IL-6 blockade with clazakizumab had shown promise in phase 2 studies (reduced donor-specific antibody and stabilized GFR), which motivated the phase 3 IMAGINE program (NCT03744910).
Study design
IMAGINE was a multicenter, double-blind, randomized, placebo-controlled trial in kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy >0 with concurrent HLA donor-specific antibody), assigning patients 1:1 to subcutaneous clazakizumab every 4 weeks or placebo. It used an event-driven design toward all-cause graft loss, with the slope of eGFR decline at 1 year as a surrogate endpoint.
Key findings
Clazakizumab failed to demonstrate the anticipated benefit, and the trial was terminated for futility at a pre-planned interim analysis. The primary efficacy outcome was not met.
Clinical implications
There is still no proven, approved pharmacologic therapy for chronic active antibody-mediated rejection. Investigator-initiated development of IL-6 pathway blockade continues with the anti–IL-6-receptor antibody tocilizumab in the smaller INTERCEPT phase 3 trial.
Category
Transplant
Source
American Journal of Transplantation
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