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
  Purpose

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


Condition Intervention Phase
Kidney Diseases
Drug: Voclosporin
Drug: tacrolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Aurinia Pharmaceuticals Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 334
Study Start Date: January 2006
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270634

  Show 45 Study Locations
Sponsors and Collaborators
Aurinia Pharmaceuticals Inc.
Investigators
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
  More Information

Publications:
Responsible Party: Aurinia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00270634     History of Changes
Other Study ID Numbers: ISA05-01
Study First Received: December 23, 2005
Results First Received: October 10, 2012
Last Updated: February 11, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

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

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

ClinicalTrials.gov processed this record on October 22, 2014