Abstract: PUB299
A Phase 1b, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Tegoprubart (AT-1501) in Patients Undergoing Kidney Transplant
Session Information
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Tchervenkov, Jean, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
- Coates, Patrick Toby, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Kadatz, Matthew J., Vancouver General Hospital, Vancouver, British Columbia, Canada
- Bornstein, Jeffrey D., Eledon Pharmaceuticals, Irvine, California, United States
- Gill, John S., St Paul's Hospital, UBC, Vancouver, British Columbia, Canada
Background
Calcineurin inhibitors (CNIs) are the backbone of kidney transplant anti-rejection therapy, and they substantially reduce the risk of acute rejection, providing excellent one-year patient and graft survival. However, only ~50% of the grafts survive 10 years, with these graft failures often being due to either late onset antibody mediated rejection or the direct nephrotoxicity of the CNIs themselves. CNIs are also associated with an increased risk of new onset diabetes after transplant, tremor, cognitive impairment, and other adverse events. As such, an agent that could produce comparable one-year results while improving long term outcomes and reducing CNI toxicities would address a significant unmet medical need. Tegoprubart (AT-1501) is a monoclonal antibody directed against the CD40 ligand (CD40L), a key mediator of co-stimulation. Inhibition of CD40L should result in a decrease in both cell and antibody mediated immunity and create a more tolerogenic immune environment. Tegoprubart has been shown to be effective in animal models and is currently being studied in kidney transplant recipients.
Methods
This pilot study will investigate the use of tegoprubart to prevent rejection in human kidney transplant recipients. Up to 12 participants will be enrolled in this open label study, and enrollment will be staggered such that the second subject cannot be screened until the first subject completes 28-days post-transplant and the DMC completes a review of the data. Adult recipients of their first allograft are eligible if they meet inclusion / exclusion criteria and if the donor kidney does not meet extended criteria, have a prolonged cold ischemia time, or come from a donor with cardiac death. All study participants will receive rATG induction therapy and a maintenance regimen of tegoprubart dosed at 20mg/kg IV every 3 weeks after a loading dose, MMF and corticosteroids. The safety of the regimen, PK of tegoprubart, and the ability of this regimen to prevent rejection will be assessed.
Results
The results will be presented when available.
Conclusion
Tegoprubart is a potential alternative to CNI in maintenance therapy for the prevention of allograft rejection in kidney transplant recipients. A Phase 1b trial to assess its safety, PK and efficacy is ongoing.
Funding
- Commercial Support – Eledon Pharmaceuticals