Phase 3 IMAGINE Trial of Clazakizumab in Kidney Transplant Rejection Fails to Meet Primary Endpoint
Key Insights
The Phase 3 IMAGINE trial, the largest placebo-controlled study in kidney transplant recipients with chronic active antibody-mediated rejection (search) (caAMR (search)), did not meet its primary efficacy outcome.
An interim analysis led to early termination of the trial, revealing no significant difference in estimated glomerular filtration rate (eGFR) between the clazakizumab and placebo groups at week 52.
Clazakizumab, an IL-6 inhibitor, had shown promise in a phase 2 trial, but the phase 3 results indicate it did not improve kidney function in caAMR (search) patients.
The Phase 3 IMAGINE trial evaluating clazakizumab in kidney transplant recipients with chronic active antibody-mediated rejection (search) (caAMR (search)) did not meet its primary endpoint. The study, which aimed to assess the efficacy of clazakizumab in preventing allograft loss or irreversible loss of allograft function, was terminated early based on an interim analysis. The results, to be presented at ASN Kidney Week 2024, highlight the challenges in treating caAMR, a significant cause of allograft loss after kidney transplantation.
The IMAGINE trial was an international, double-blind, placebo-controlled study designed to enroll approximately 350 kidney transplant recipients with caAMR (search). Participants were randomized 1:1 to receive either clazakizumab or placebo. The trial's primary outcome was time to a composite of all-cause allograft loss or irreversible loss of allograft function, with the 1-year estimated glomerular filtration rate (eGFR) slope accepted by the FDA as a reasonably likely surrogate endpoint.
Interim Analysis and Early Termination
An interim analysis was conducted after approximately 100 participants completed one year of the study. Independent investigators determined that the trial was unlikely to meet its primary efficacy outcome. Consequently, the data and safety monitoring board recommended stopping the study.
Final Analysis of eGFR
The final analysis, conducted after the early termination, revealed no statistically significant difference in the Least Squares mean change from baseline in eGFR at week 52 between the clazakizumab and placebo groups. This indicates that clazakizumab did not provide a significant benefit in preserving kidney function in patients with caAMR (search) compared to placebo. No safety concerns were observed during the study.
Expert Commentary
"Treating patients with caAMR (search) remains a challenge, and while we are disappointed by these results, we will continue to advance research for kidney transplant patients," said Arjang Djamali, MD, corresponding author from Maine Medical Center. He also expressed gratitude to the patients, research sites, and CSL (search), the study sponsor, for their commitment to addressing the unmet needs of these patients.
The study is titled: "Clazakizumab in Chronic Active Antibody-Mediated Kidney Transplant Rejection: Results of the IMAGINE Phase 3 Study"