title: The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation.
abstract: 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 (r(2) = 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.
authors.affiliation: Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. sbusque@stanford.edu
authors.forename: S
authors.initials: S
authors.lastname: Busque
authors.forename: M
authors.initials: M
authors.lastname: Cantarovich
authors.forename: S
authors.initials: S
authors.lastname: Mulgaonkar
authors.forename: R
authors.initials: R
authors.lastname: Gaston
authors.forename: A O
authors.initials: AO
authors.lastname: Gaber
authors.forename: P R
authors.initials: PR
authors.lastname: Mayo
authors.forename: S
authors.initials: S
authors.lastname: Ling
authors.forename: R B
authors.initials: RB
authors.lastname: Huizinga
authors.forename: H-U
authors.initials: HU
authors.lastname: Meier-Kriesche
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D016572:Cyclosporine / Q000009:adverse effects*; D048909:Diabetes Complications / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D006085:Graft Survival; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; C484071:voclosporin; D016572:Cyclosporine; D016559:Tacrolimus