A recent phase 3 Kidney Transplant trial investigating the effects of clazakizumab, a monoclonal antibody targeting interleukin-6 (IL-6), has concluded with disappointing results for patients with chronic active antibody-mediated rejection (caAMR) following kidney transplants. CaAMR is a critical issue in kidney transplantation, leading to allograft loss and lacking approved therapeutic options. Building on earlier phase 2 trials where clazakizumab appeared to stabilize kidney function in transplant recipients, researchers launched the IMAGINE Phase 3 Kidney Transplant trial to examine its efficacy more rigorously. This trial, the largest placebo-controlled study to date on clazakizumab for caAMR, aimed to determine if the drug could effectively protect transplant recipients from allograft failure. Findings from this trial were presented at the American Society of Nephrology’s (ASN) Kidney Week 2024, held from October 23 to 27.
Trial Design and Early Analysis
The IMAGINE study was an international, double-blind, placebo-controlled trial involving roughly 350 kidney transplant recipients diagnosed with caAMR. Participants were divided randomly, with half receiving clazakizumab and the other half a placebo. This trial marked a milestone in transplant research, as it was the first in transplantation to use a surrogate endpoint approved by the U.S. Food and Drug Administration. The primary endpoint focused on the change in the estimated glomerular filtration rate (eGFR) after one year, providing a reliable measure of kidney function over time. However, an interim analysis conducted on data from about 100 participants indicated that the trial was unlikely to meet its primary endpoint of delaying allograft loss or maintaining kidney function. Consequently, an independent safety board recommended discontinuing the study.
Final Results and Future Implications
Upon final analysis, researchers found no significant difference in kidney function between the clazakizumab and placebo groups, as indicated by the Least Squares mean change in eGFR over 52 weeks. Importantly, no safety issues emerged, suggesting clazakizumab is generally safe for patients, but ultimately ineffective in improving kidney outcomes for those with caAMR. The study, titled “Clazakizumab in Chronic Active Antibody-Mediated Kidney Transplant Rejection: Results of the IMAGINE Phase 3 Phase 3 Kidney Transplant Study,” highlights the continued challenge of finding effective therapies for caAMR and underscores the need for ongoing research into alternative treatments for post-transplant kidney health.
