TY - JOUR
T1 - The PROMISE study
T2 - A phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de Novo kidney transplantation
AU - Busque, S.
AU - Cantarovich, M.
AU - Mulgaonkar, S.
AU - Gaston, R.
AU - Gaber, A. O.
AU - Mayo, P. R.
AU - Ling, S.
AU - Huizinga, R. B.
AU - Meier-Kriesche, H. U.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2011/12
Y1 - 2011/12
N2 - Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor being developed for organ transplantation. PROMISE was a 6-month, multicenter, randomized, open-label study of three ascending concentration-controlled groups of VCS (low, medium and high) compared to tacrolimus (TAC) in 334 low-risk renal transplant recipients. The primary endpoint was demonstration of noninferiority of biopsy proven acute rejection (BPAR) rates. Secondary objectives included renal function, new onset diabetes after transplantation (NODAT), hypertension, hyperlipidemia and pharmacokinetic-pharmacodynamic evaluation. The incidence of BPAR in the VCS groups (10.7%, 9.1% and 2.3%, respectively) was noninferior to TAC (5.8%). The incidence of NODAT for VCS was 1.6%, 5.7% and 17.7% versus 16.4% in TAC (low-dose VCS, p = 0.03). Nankivell estimated glomerular filtration rate was respectively: 71, 72, 68 and 69 mL/min, statistically lower in the high-dose group, p = 0.049. The incidence of hypertension and adverse events was not different between the VCS groups and TAC. VCS demonstrated an excellent correlation between trough and area under the curve (r2= 0.97) and no difference in mycophenolic acid exposure compared to TAC. This 6-month study shows VCS to be as efficacious as TAC in preventing acute rejection with similar renal function in the low- and medium-exposure groups, and potentially associated with a reduced incidence of NODAT.
AB - Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor being developed for organ transplantation. PROMISE was a 6-month, multicenter, randomized, open-label study of three ascending concentration-controlled groups of VCS (low, medium and high) compared to tacrolimus (TAC) in 334 low-risk renal transplant recipients. The primary endpoint was demonstration of noninferiority of biopsy proven acute rejection (BPAR) rates. Secondary objectives included renal function, new onset diabetes after transplantation (NODAT), hypertension, hyperlipidemia and pharmacokinetic-pharmacodynamic evaluation. The incidence of BPAR in the VCS groups (10.7%, 9.1% and 2.3%, respectively) was noninferior to TAC (5.8%). The incidence of NODAT for VCS was 1.6%, 5.7% and 17.7% versus 16.4% in TAC (low-dose VCS, p = 0.03). Nankivell estimated glomerular filtration rate was respectively: 71, 72, 68 and 69 mL/min, statistically lower in the high-dose group, p = 0.049. The incidence of hypertension and adverse events was not different between the VCS groups and TAC. VCS demonstrated an excellent correlation between trough and area under the curve (r2= 0.97) and no difference in mycophenolic acid exposure compared to TAC. This 6-month study shows VCS to be as efficacious as TAC in preventing acute rejection with similar renal function in the low- and medium-exposure groups, and potentially associated with a reduced incidence of NODAT.
KW - Acute rejection
KW - calcineurin inhibitor agents
KW - clinical trials
KW - new onset diabetes mellitus
KW - pharmacodynamics of immunosuppressive agents
KW - pharmacokinetics of immunosuppressive agents
KW - renal transplant
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U2 - 10.1111/j.1600-6143.2011.03763.x
DO - 10.1111/j.1600-6143.2011.03763.x
M3 - Article
C2 - 21943027
AN - SCOPUS:82455171878
VL - 11
SP - 2675
EP - 2684
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 12
ER -