Belatacept as a Replacement for CNIs 3 to 12 Months Post-transplantation in Patients With Early Graft Dysfunction

Condition(s) studied

Investigational drug(s) / intervention(s)

Belatacept 250 Milligram Intravenous Powder for Solution: Phase 1 (from 3 to 12 months post transplantation): conversion to belatacept (IV, 5mg/Kg days 1, 15,30, 45, 60 then every months) and CNI withdrawal. Phase 2 (from 12 to 18 months post transplantation) : belatacept arrest and CNI resumption (tacrolimus target 6 ng/ml)

Study summary

Calcineurin inhibitors (CNI) remain the standard treatment in renal transplantation to prevent rejection. Currently the main limitation of kidney transplantation is the occurrence of chronic graft dysfunction due to the CNI nephrotoxicity. Thus, strategies to minimize or stop CNI have been developed as belatacept, a fusion protein (CTLA4-Ig) blocking the ligand of the main CD28 costimulatory molecule. In the original phase III trial, used de novo in combination with MMF (without CNI) belatacept allowed to obtain a better renal function as soon as 1 year and a better graft and patient survival after 7 years. Despite these excellent results, belatacept has not become the gold standard due to a higher incidence of early rejection. In addition, belatacept is not covered by the french social security policy, because benefits are considered insufficient with respect to the cost. Patients with poor early graft function are a preferred indication of belatacept. It is then used instead of CNI at 3 months post-transplant allowing to improve kidney function without over-risk of rejection. Currently after conversion, belatacept is maintained indefinitely due to the supposed CNI chronic nephrotoxicity. However this one is more and more questionable. Thus, the investigators assume that in patients with poor function at 3 months posttransplantation the belatacept's benefit could be obtained by a transient replacement of CNI by belatacept from 3 to 12 months post-transplantation. It is the feasibility of this strategy and its medico-economic impact that the investigators wish to study.

Eligibility

Primary outcome measure(s)

• Feasibility of a transient replacement of CNIs by belatacept in renal transplant patients with early graft dysfunction. Creatinine clearance did not decrease by more than 25% from the cessation of belatacept 6 months after reintroduction of CNI. — Month 15
  Feasibility was defined by preserved renal function and good tolerance 6 months after reintroduction of CNI. Renal function was defined as preserved if creatinine clearance (according to Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI)) did not decrease by more than 25% from the cessation of belatacept. The good tolerance of CNI was defined by the absence of complications leading to the cessation of treatment.

Trial sites (1)

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