The PROMISE study: A phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de Novo kidney transplantation

S. Busque, M. Cantarovich, S. Mulgaonkar, R. Gaston, A. O. Gaber, P. R. Mayo, S. Ling, R. B. Huizinga, H. U. Meier-Kriesche

Research output: Contribution to journalArticle

43 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)2675-2684
Number of pages10
JournalAmerican Journal of Transplantation
Volume11
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • Acute rejection
  • calcineurin inhibitor agents
  • clinical trials
  • new onset diabetes mellitus
  • pharmacodynamics of immunosuppressive agents
  • pharmacokinetics of immunosuppressive agents
  • renal transplant

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'The PROMISE study: A phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de Novo kidney transplantation'. Together they form a unique fingerprint.

Cite this