Kidney Week

Abstract: SA-OR84

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

Session Information

• Transplantation: Clinical Management and Monitoring
  October 26, 2024 | Location: Room 25, Convention Center
  Abstract Time: 04:50 PM - 05:00 PM

Category: Transplantation

• 2102 Transplantation: Clinical

Authors

• Djamali, Arjang, Maine Medical Center, Portland, Maine, United States

Arjang Djamali, MD, MS, FASN

• Bohmig, Georg, Medical University of Vienna, Vienna, Austria

Georg Bohmig, MD

• Chadban, Steven J., Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

Steven J. Chadban, MBBS, PhD

• Kumar, Deepali, University of Toronto, Toronto, Ontario, Canada

Deepali Kumar, MD, MSc

• Mannon, Roslyn B., University of Nebraska Medical Center, Omaha, Nebraska, United States

Roslyn B. Mannon, MD, FASN

• van Gelder, Teun, Leiden University Medical Center, Leiden, Netherlands

Teun van Gelder, MD

• Schultz-Hauser, Gabriele, CSL Behring, Marburg, Germany

Gabriele Schultz-Hauser, PhD

• Alperovich Lehrer, Gabriela, CSL Vifor, Madrid, Spain

Gabriela Alperovich Lehrer

• Preiss, Ralph, CSL Behring, Berne, Switzerland

Ralph Preiss, MD

• Raychaudhuri, Aparna, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Aparna Raychaudhuri, PhD

• Lee, Laurie, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Laurie Lee, MD

• Nickerson, Peter W., University of Manitoba, Winnipeg, Manitoba, Canada

Peter W. Nickerson, MD

Background

Chronic active antibody-mediated rejection (caAMR) is a common cause of graft loss after kidney transplant with no approved therapies. Clazakizumab, a high-affinity, humanized monoclonal antibody that binds IL-6, decreased donor-specific antibody (DSA) production and microvascular inflammation and stabilized eGFR in a phase 2 study in kidney transplant recipients (KTRs) with caAMR.

Methods

IMAGINE (NCT03744910; start date: Oct 2019), a global (66 sites) double-blind phase 3 study, aimed to recruit ~350 KTRs with caAMR determined by kidney biopsy based on Banff 2015 criteria. KTRs were randomized 1:1 to clazakizumab (12.5 mg SC q4w) or placebo. Primary endpoint was time to all-cause graft loss (return to dialysis, graft nephrectomy, re-transplantation, eGFR <15 mL/min/1.73m², death from any cause or sustained 40% reduction in eGFR). 1-yr eGFR was accepted as a reasonably likely surrogate endpoint (RLSE) for accelerated approval by the FDA. Temporary dose reduction was allowed at investigator discretion. This interim analysis (IA) was conducted when ~100 KTRs completed 1 yr of study participation.

Results

At the time of the IA, 194 KTRs had been enrolled, and 115 were followed for 52 weeks for eGFR change from baseline. The analysis indicated that the study was unlikely to meet the primary efficacy outcome (time to composite all-cause allograft loss or irreversible loss of allograft function), and the data and safety monitoring board recommended to stop the study. No gastrointestinal perforations or other safety concerns were noted.

Conclusion

Despite encouraging phase 2 results, the data from the IMAGINE IA did not support continuation. Nonetheless, this was the largest placebo-controlled study in KTRs with caAMR and was first transplant study for which the FDA accepted a 1-yr eGFR slope as a RLSE. No safety concerns were noted. Detailed primary analyses will be presented after the database has been unblinded prior to ASN Kidney Week.

Funding

• Commercial Support – CSL Behring