ISA247: A Phase IIb Multicenter, Open Label, Concentration-Controlled Trial in De Novo Renal Transplantation.
A. O. Gaber, S. Busque, S. Mulgaonkar, R. Gaston, A. Jevnikar, H.-U. Meier-Kriesche. The Methodist Hospital; Stanford School of Medicine; St. Barnabas Medical Center; University of Alabama Birmingham; London Health Sciences Centre; University of Florida.
Background: ISA247 is a novel calcineurin inhibitor (CNi), developed using a pharmacodynamic approach for use in autoimmune disease and solid organ transplantation. In moderate to severe plaque psoriasis, a Canadian Phase III trial has demonstrated that ISA247 is efficacious with minimal changes to renal function and a European trial is presently underway comparing ISA247 to cyclosporine A (CsA). In renal transplantation, a Phase IIa study comparing ISA247 to CsA in stable renal transplant recipients demonstrated ISA247 to be efficacious and well tolerated. A Phase IIb study in de novo renal transplant patients comparing ISA247 to tacrolimus is ongoing and final data will be available May 2008. We hypothesize that ISA247 is non-inferior to tacrolimus in terms of efficacy.
Methods: This is a 6 month, randomized, multicenter, open-label, concentration-controlled study comparing three oral ISA247 dosing groups (0.4, 0.6, or 0.8 mg/kg bid) to tacrolimus in 42 North American transplant centres. All CNis were titrated to target trough concentrations. Inclusion criteria included males and (non-pregnant) females between the ages of 18-65 who were receiving a first deceased or living donor renal transplant. Cold ischemia times were to be 24 hours, and peak panel reactive antibodies 30%. The primary efficacy parameter of the trial is non-inferiority (in at least one dose group) in biopsy proven acute rejection (BPAR) at 6 months as compared to tacrolimus. Secondary objectives include: renal function; PK/PD relationships; patient and graft survival; and proportion of patients with hypertension, hyperlipidemia or new onset diabetes mellitus (NODM).
Results: Interim data, as previously presented at the 2007 ATC, demonstrated that ISA247 had rejection rates similar to tacrolimus (ISA247 0.4 mg/kg bid 11%, ISA247 0.6 mg/kg bid 8%, ISA247 0.8 mg/kg bid 3%, tacrolimus 9%) and confirmed previous results indicating an improved safety profile. 334 patients have now been enrolled between January 2006 and June 2007, with an optional extension to 12 months added to the trial. A recent approval by both FDA and Health Canada has allowed continued use of ISA247 in these patients until commercialization. The six month final results will be available for presentation at ATC 2008.
Keywords: Immunosuppression; Kidney transplantation; Efficacy; Safety
Session Information
Session Title: : Late-Breaking Abstract Session (4:00 PM-5:00 PM)
Date: Tuesday, June 3, 2008 - 4:50 PM
Location: Room 801 B
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