by American Society of Nephrology

Credit: Pixabay/CC0 Public Domain

Chronic active antibody-mediated rejection (caAMR) is a common cause of allograft loss after transplantation, with no approved therapies. Clazakizumab, a monoclonal antibody that targets the inflammatory cytokine interleukin-6 (IL-6), stabilized kidney transplant recipients' kidney function in a Phase II trial. Investigators now have data from a Phase III trial with clazakizumab.

The findings from the Phase III IMAGINE trial, the largest placebo-controlled study in kidney transplant recipients with caAMR, were presented at ASN Kidney Week 2024 October 23–27.

The international IMAGINE double-blind Phase III trial was the first study in transplantation to have a reasonably likely surrogate endpoint (one-year estimated glomerular filtration rate [eGFR] slope—a measure of changes in kidney function) accepted by the U.S. Food and Drug Administration. The trial aimed to recruit approximately 350 kidney transplant recipients with cAMR, randomized 1:1 to clazakizumab or placebo.

In an interim analysis conducted when approximately 100 participants completed one year of the study, independent investigators found that the study was unlikely to meet the primary efficacy outcome (time to a composite of all-cause allograft loss or irreversible loss of allograft function), and the data and safety monitoring board recommended to stop the study.

The final analysis following early termination after one-year interim analysis of eGFR showed that there was no difference in Least Squares mean change from baseline in eGFR at week 52 for clazakizumab compared with placebo. There were no safety concerns observed in the study.

"Treating patients with caAMR remains a challenge, and while we are disappointed by these results, we will continue to advance research for kidney transplant patients," said corresponding author Arjang Djamali, MD, of Maine Medical Center.

"We want to extend our gratitude to all those involved in the trial, including our patients, research sites and study sponsor, CSL, for their commitment to addressing the unmet needs of these patients."

More information: Study: "Clazakizumab in Chronic Active Antibody-Mediated Kidney Transplant Rejection: Results of the IMAGINE Phase 3 Study"

Provided by American Society of Nephrology