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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00270634
Recruitment Status : Completed
First Posted : December 28, 2005
Results First Posted : February 12, 2013
Last Update Posted : February 12, 2013
Information provided by (Responsible Party):
Aurinia Pharmaceuticals Inc.

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

Condition or disease Intervention/treatment Phase
Kidney Diseases Drug: Voclosporin Drug: tacrolimus Phase 2

Detailed Description:

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIb, Randomized, Multicenter, Open-Label, Concentration Controlled, Safety Study of ISA247 (Voclosporin) and Tacrolimus (Prograf®) in De Novo Renal Transplant Patients
Study Start Date : January 2006
Actual Primary Completion Date : July 2009
Actual Study Completion Date : July 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Low Dose Voclosporin
Low dose voclosporin
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
Active Comparator: Mid Dose Voclosporin
Mid Dose Voclosporin
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
Active Comparator: High Dose Voclosporin
High Dose Voclosporin
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
Active Comparator: Tacrolimus
Standard Dose Tacrolimus
Drug: tacrolimus
tacrolimus 0.05 mg/kg po BID

Primary Outcome Measures :
  1. Biopsy Proven Acute Rejection (BPAR) [ Time Frame: Six months ]
    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.

Secondary Outcome Measures :
  1. To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR) [ Time Frame: Six months ]
    ANOVAs to test for differences in GFR at Month 6.

  2. The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition [ Time Frame: Six months ]

    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.

  3. Patient Survival [ Time Frame: Six months ]
  4. Graft Survival [ Time Frame: Six months ]
  5. Hypertension, Hyperlipidemia, or Hyperglycemia [ Time Frame: Six months ]
  6. A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up. [ Time Frame: Six months ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00270634

  Show 45 Study Locations
Sponsors and Collaborators
Aurinia Pharmaceuticals Inc.
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

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Aurinia Pharmaceuticals Inc. Identifier: NCT00270634     History of Changes
Other Study ID Numbers: ISA05-01
First Posted: December 28, 2005    Key Record Dates
Results First Posted: February 12, 2013
Last Update Posted: February 12, 2013
Last Verified: February 2013

Keywords provided by Aurinia Pharmaceuticals Inc.:
Randomized Controlled Trials
Kidney Transplantation
Treatment Outcome

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents