Abstract: SA-OR88
First-in-Human Phase 2a (ATMIRe) Trial of Ex Vivo Allograft Treatment with iCM012 to Mitigate Ischemia-Reperfusion Injury in Kidney Transplantation
Session Information
- Transplantation: Clinical Management and Monitoring
October 26, 2024 | Location: Room 25, Convention Center
Abstract Time: 05:30 PM - 05:40 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Biglarnia, Ali Reza, Lunds Universitet, Malmö, Sweden
- Nilsson, Bo, Uppsala universitet Rudbecklaboratoriet, Uppsala, Sweden
- Raihle, Carl J., Skanes universitetssjukhus Malmo, Malmo, Skåne, Sweden
- Slivca, Oleg, Skanes universitetssjukhus Malmo, Malmo, Skåne, Sweden
- Paul, Clara H., Skanes universitetssjukhus Malmo, Malmo, Skåne, Sweden
Background
iCM012 is an amphiphilic polymer that forms a dense protective coat on cell surfaces. In porcine transplant studies, ex vivo administration of iCM012 to kidney allografts produced a robust but transient non-toxic cell coating that consistently mitigated ischemia-reperfusion injury (IRI)-induced early thromboinflammation, reduced late systemic cytokine release, and improved allograft function. A first-in-human trial evaluated the safety and tolerability of iCM012 in clinical kidney transplantation.
Methods
A phase IIa, randomized, double-blind, placebo-controlled trial (NCT05246618) was conducted at a single center in Sweden, enrolling 18 de novo kidney transplant patients. Participants were randomized 2:1 to receive either iCM012 (n=12) or placebo (n=6). iCM012 was administered ex vivo to the retrieved kidney allografts as a single arterial infusion by gravity at the end of organ preservation. Primary endpoints were safety and tolerability over 12 months. Secondary endpoints included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR) at 12 months. Urine and plasma samples were collected for exploratory analysis.
Results
Patient characteristics were balanced between the groups; however, the median Kidney Donor Profile Index was higher in the iCM012 group compared to placebo (76 [32-97] vs. 41 [30-94], P=0.062). There were no differences in cold ischemic time or use of continuous machine perfusion between groups. No DGF occurred and all transplanted kidneys showed excellent primary function, even one iCM012-treated kidney with a CIT of 25.7 hours that experienced technical complications, resulting in prolonged warm ischemia and re-anastomosis. In the iCM012 group, innate immune activation (sC5b-9) and tubular injury markers (IL-18, KIM-1, NGAL, Cystatin-C, and L-FABP) were at lower levels in 24-hour urine samples on day 1. At 12 months, there was no difference in median relative eGFR between the iCM012 and placebo groups (42 [32-58] vs. 45.5 [32-72]).
Conclusion
iCM012 demonstrated a favorable safety profile and showed promising efficacy in mitigating IRI and preserving allograft function within a 12-month follow-up. These findings strongly support further investigation in larger, multicenter trials to confirm its therapeutic potential in kidney transplantation.
Funding
- Commercial Support – iCoat Medical