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Kidney Week

Abstract: FR-PO1203

Application of the IBox Clinical Trial Simulation Tool to Project Long-Term Kidney Allograft Outcome in the TRANSFORM Study

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Divard, Gillian, INSERM U970, Paris, France
  • Aubert, Olivier, INSERM U970, Paris, France
  • Raynaud, Marc, INSERM U970, Paris, France
  • Pascual, Julio, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
  • Bernhardt, Peter, Novartis Pharma AG, Basel, Switzerland
  • Legendre, Christophe M., INSERM U970, Paris, France
  • Loupy, Alexandre, INSERM U970, Paris, France

Group or Team Name

  • Paris Transplant Group
Background

Development of pharmaceutical agents in transplant is currently limited by long waits for hard endpoints. We sought to use a risk stratification system in a randomized control trial (RCT) and determine individual patient long-term graft survival.

Methods

We used validated data from TRANSFORM trial (NCT01950819), a RCT that compares KTR to receive everolimus with low-exposure CNI or mycophenolic acid (MPA) with standard-exposure CNI. We applied the iBox (NCT03474003), an integrative and validated risk score which used parameters measured at 1 year after randomization and projected patients individual long-term allograft survival.

Results

A total of 1855 patients (930 with everolimus and 925 with MPA) reached the 1 year after transplant primary endpoint. Mean eGFR was 55.9±19.7 mL/min/1.73m2 with everolimus vs 56.1±19.1 with MPA. Mean protein/creatinin ratio was 0.32±0.67 g/g vs 0.26±0.63 with MPA. The incidence of BPAR was of 2.5% with everolimus vs 3.6% with MPA. The rate of DSA was 13.7% with everolimus vs 15.9% with MPA. These immunological, functional and histological parameters were entered into the iBox, which translated to an overall patient graft survival at 3, 5 and 10 years after randomization of 94.2% vs 94.7%, 91.2% vs 92.0% and 83.3% vs 84.9% in the everolimus and MPA arms respectively (95%CI -3.1% to 0.2% below the non-inferiority margin of 10%) Figure.

Conclusion

The iBox system confirms the non-inferiority of everolimus vs MPA 10 years after patient's randomization in the RCT. Given the unmet need for surrogate endpoint for clinical trials, this study shows the potential of a clinical trial simulation tool to fast track the development and approval of pharmaceutical agents.