Clazakizumab for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients: Phase 3 IMAGINE Study Design

P. Nickerson¹, G. Böhmig², S. Chadban³, D. Kumar⁴, R. B. Mannon⁵, T. van Gelder⁶, S. Adler⁷, E. Chong⁷, A. Djamali⁸

¹University of Manitoba, Winnipeg, MB, Canada, ²Medical University of Vienna, Vienna, Austria, ³University of Sydney, Sydney, Australia, ⁴University of Toronto, Toronto, ON, Canada, ⁵University of Nebraska Medical Center, Omaha, NE, ⁶Leiden University Medical Center, Leiden, Netherlands, ⁷CSL Behring, King of Prussia, PA, ⁸University of Wisconsin, Madison, WI

Meeting: 2021 American Transplant Congress

Abstract number: 1047

Keywords: Graft failure, Kidney/liver transplantation

Topic: Clinical Science » Kidney » Kidney Chronic Antibody Mediated Rejection

Session Information

Session Name: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Chronic active antibody-mediated rejection (CAMR) is a major cause of allograft loss with no approved drugs for its treatment. Currently, off-label regimens recommended by experts based on small clinical trials are used, reflecting the high unmet medical need for effective therapies based on well-controlled trials. Clazakizumab (CLAZA) is a high-affinity, humanized monoclonal antibody that binds IL-6 and blocks inflammation and antibody production. Small Phase 2 studies of CLAZA in kidney transplant recipients with CAMR suggest early modulation of donor-specific antibodies (DSA), stabilization of GFR, and a manageable safety profile. In CAMR, a progressive decline in kidney function is, by definition, on the pathway to graft loss. Here, we report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of CLAZA for the treatment of CAMR.

*Methods: IMAGINE is a multi-center, double-blind trial of 350 kidney transplant recipients with CAMR (Banff cg>0 with human leukocyte antigen DSA) randomized 1:1 to receive CLAZA (12.5 mg subcutaneous once every 4 weeks) or placebo (Fig). The event-driven trial design will follow pts for 5 years or until 221 occurrences of graft loss (primary endpoint); defined as return to dialysis, graft nephrectomy, retransplantation, eGFR <15 mL/min/1.73m², or death from any cause. A surrogate for graft loss, eGFR slope at 1 year, will be assessed based on prior modelling validation¹. Secondary endpoints will include measures of PK/PD and PROs.

*Results: Recruitment is ongoing across sites in N. America, Europe, Asia, and Australia.

*Conclusions: Currently, no treatment has proven effective in CAMR. This pivotal Phase 3 trial includes prognostic biomarker enrichment and uniquely incorporates a surrogate endpoint for graft loss, eGFR slope at 1 year, which may accelerate the approval of a novel therapy for patients at risk of allograft loss.

References

1. Irish W. et al. Transplantation. 2020; Epub ahead of print. doi: 10.1097/TP.0000000000003274.

To cite this abstract in AMA style:

Nickerson P, Böhmig G, Chadban S, Kumar D, Mannon RB, Gelder Tvan, Adler S, Chong E, Djamali A. Clazakizumab for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients: Phase 3 IMAGINE Study Design [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/clazakizumab-for-the-treatment-of-chronic-active-antibody-mediated-rejection-in-kidney-transplant-recipients-phase-3-imagine-study-design/. Accessed November 22, 2024.

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