Study of ISA247 (Voclosporin) in De Novo Renal Transplantation (PROMISE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aurinia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT00270634
First received: December 23, 2005
Last updated: February 11, 2013
Last verified: February 2013

December 23, 2005
February 11, 2013
January 2006
July 2009   (final data collection date for primary outcome measure)
Biopsy Proven Acute Rejection (BPAR) [ Time Frame: Six months ] [ Designated as safety issue: No ]
The primary objective of the PROMISE trial was to demonstrate noninferiority of biopsy proven acute rejection (BPAR) rate in de novo renal transplant patients at 6 months in at least one VCS treatment group.
Biopsy proven acute rejection (BPAR) at six months
Complete list of historical versions of study NCT00270634 on ClinicalTrials.gov Archive Site
  • To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR) [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
    ANOVAs to test for differences in GFR at Month 6.
  • The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition [ Time Frame: Six months ] [ Designated as safety issue: No ]

    A sparse sampling protocol of whole blood samples obtained on Day 180 at time points immediately prior to drug administration and at 1, 2, and 4 hours post‐dose were utilized.

    Standard non‐compartmental analysis (NCA) was performed on whole blood concentration data for voclosporin and its metabolites, tacrolimus, MPA (mycophenolic acid) and MPAG (mycophenolic acid glucuronide). Tmax and Cmax were obtained directly from the concentration‐time profiles without interpolation. AUC(0‐4)[area under the curve] was calculated using log‐linear trapezoidal rule. Cmax, AUC(0‐4), C0 and C2 were summarized using descriptive statistics.

  • Patient Survival [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  • Graft Survival [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  • Hypertension, Hyperlipidemia, or Hyperglycemia [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  • A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up. [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  • • To demonstrate a 5% improvement in renal function at 6 months as measured by Nankivell GFR.
  • • To determine the pharmacokinetic–pharmacodynamic relationship between ISA247 and calcineurin inhibition, or tacrolimus and calcineurin inhibition.
  • • To determine patient survival at 6 months.
  • • To determine graft survival at 6 months.
  • • To determine the proportion of patients with hypertension, hyperlipidemia, or hyperglycemia at 6 months.
  • • A composite of biopsy-proven chronic rejection graft loss, death, or lost to follow up.
  • • A composite of biopsy-proven acute rejections, graft loss or death.
  • • To establish the safety of ISA247.
Not Provided
Not Provided
 
Study of ISA247 (Voclosporin) in De Novo Renal Transplantation
A Phase IIb, Randomized, Multicenter, Open-Label, Concentration Controlled, Safety Study of ISA247 (Voclosporin) and Tacrolimus (Prograf®) in De Novo Renal Transplant Patients

This study will see if voclosporin is safe and effective in preventing kidney transplant rejection.

Prograf® (tacrolimus) is associated with numerous side effects, including neurotoxicity, nephrotoxicity, polyoma nephropathy, QT prolongation, and New Onset Diabetes Mellitus After Transplant (NODAT). Voclosporin is a novel calcineurin inhibitor intended for use in the prevention of organ graft rejection.

Comparison(s): Voclosporin at 3 dose levels (0.4, 0.6, and 0.8 mg/kg twice a day) compared to tacrolimus

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Kidney Diseases
  • Drug: Voclosporin
    voclosporin 0.4, 0.6, 0.8 mg/kg po BID
    Other Name: ISA247
  • Drug: tacrolimus
    tacrolimus 0.05 mg/kg po BID
  • Active Comparator: Low Dose Voclosporin
    Low dose voclosporin
    Intervention: Drug: Voclosporin
  • Active Comparator: Mid Dose Voclosporin
    Mid Dose Voclosporin
    Intervention: Drug: Voclosporin
  • Active Comparator: High Dose Voclosporin
    High Dose Voclosporin
    Intervention: Drug: Voclosporin
  • Active Comparator: Tacrolimus
    Standard Dose Tacrolimus
    Intervention: Drug: tacrolimus

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
334
July 2009
July 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and females aged 18 - 65 years inclusive at the time of screening.
  • Patients must be receiving a first cadaveric or living donor renal transplant.
  • Patients must be able to receive oral medication at time of randomization.
  • Females who are not pregnant or nursing or planning to become pregnant during the course of the study, or 3 months after last dose of study medication.
  • Sexually-active women of child-bearing potential (including those who are < 1 year postmenopausal) and sexually-active men who are practicing a highly effective method of birth control. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly and will include implants, injectables, combined oral contraceptives, double-barrier method, sexual abstinence, or a sterile partner. Sexually-active men and women of child-bearing potential should continue to practice contraception as outlined above during treatment and for ≥ 3 months after the last dose of voclosporin.
  • Able to give written informed consent prior to screening procedures.
  • Able to keep study appointments and cooperate with all study requirements, in the opinion of the investigator.

Exclusion Criteria:

  • Receiving a HLA (human leukocyte antigen)identical living related transplant.
  • Cold ischemic time > 24 hours.
  • Peak PRA (panel reactive antibodies) > 30%
  • Cadaveric donors who are over age 60, non-heart beating donors, or any cadaveric donors positive for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Transplantation of multiple grafts (e.g. kidney and pancreas).
  • Systemic infections requiring continued therapy at the time of entry into this study. (Prophylaxis against cytomegalovirus [CMV] and/or pneumocystis carinii pneumonia (PCP) infection will be permitted).
  • Serologic evidence or known latent human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) virus. Known negative serology prior to study entry may be used.
  • A current malignancy or history of malignancy within 5 years or a history of lymphoma at any time. Subjects can be enrolled with a history of squamous or basal cell carcinoma that has been surgically excised or removed with curettage and electrodesiccation.
  • Requires prohibited medications or treatment during the study.
  • Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl transferase (GGT) ≥ 3x upper limit of normal (ULN) at time of transplantation.
  • White blood cell count ≤ 2.8 x 10^9/L.
  • Triglycerides ≥ 3x ULN.
  • Pregnant women or nursing mothers.
  • Has used any investigational drug or device within 28 days or 5 half lives (whichever is longer) prior to enrollment.
  • Previous exposure to voclosporin.
  • A history of active alcoholism or drug addiction within 1 year prior to study entry.
  • Weighs < 45 kg (99 lbs) or > 140 kg (308 lbs).
  • A history of disease, including mental/emotional disorder that would interfere with the subject's participation in the study, or that might cause the administration of voclosporin to pose a significant risk to the subject, in the opinion of the investigator.
  • Allergy to iodine.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00270634
ISA05-01
Yes
Aurinia Pharmaceuticals Inc.
Aurinia Pharmaceuticals Inc.
Not Provided
Study Director: Daniel Abramowicz, MD, PhD Erasme Hospital
Study Director: Philip Belitsky, MD No Affiliation
Study Director: Arthur Matas, MD University of Minnesota - Clinical and Translational Science Institute
Study Director: Mark Pescovitz, MD Indiana University
Study Director: A. Osama Gaber, MD The Methodist Hospital System
Aurinia Pharmaceuticals Inc.
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP