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

February 11, 2013 updated by: Aurinia Pharmaceuticals Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

334

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • Isotechnika Investigational Site
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • Isotechnika Investigational Site
      • Toronto, Ontario, Canada, M5C 2T2
        • Isotechnika Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H3A 1A1
        • Isotechnika Investigational Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7M 0Z9
        • Isotechnika Investigational Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35924
        • Isotechnika Investigational Site
    • California
      • Los Angeles, California, United States, 90033
        • Isotechnika Investigational Site
      • Los Angeles, California, United States, 90057
        • Isotechnika Investigational Site
      • Los Angeles, California, United States, 90095-7306
        • Isotechnika Investigational Site
      • Orange, California, United States, 92868
        • Isotechnika Investigational Site
      • Palo Alto, California, United States, 94304-1510
        • Isotechnika Investigational Site
      • San Diego, California, United States, 92123
        • Isotechnika Investigational Site
      • San Francisco, California, United States, 94143-0116
        • Isotechnika Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80262
        • Isotechnika Investigational Site
    • Florida
      • Gainesville, Florida, United States, 32610
        • Isotechnika Investigational Site
      • Tampa, Florida, United States, 33606
        • Isotechnika Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Isotechnika Investigational Site
      • Chicago, Illinois, United States, 60637
        • Isotechnika Investigational Site
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Isotechnika Investigational Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Isotechnika Investigational Site
      • New Orleans, Louisiana, United States, 70121
        • Isotechnika Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Isotechnika Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Isotechnika Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-9623
        • Isotechnika Investigational Site
      • Detroit, Michigan, United States, 48202
        • Isotechnika Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Isotechnika Investigational Site
    • New Jersey
      • Livingston, New Jersey, United States, 07039
        • Isotechnika Investigational Site
    • New York
      • Buffalo, New York, United States, 14203
        • Isotechnika Investigational Site
      • Hawthorne, New York, United States, 10532
        • Isotechnika Investigational Site
      • New York, New York, United States, 10021
        • Isotechnika Investigational Site
      • Rochester, New York, United States, 14642-8410
        • Isotechnika Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Isotechnika Investigational Site
      • Winston-Salem, North Carolina, United States, 27157
        • Isotechnika Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Isotechnika Investigational Site
      • Cincinnati, Ohio, United States, 45267-0585
        • Isotechnika Investigational Site
    • Oregon
      • Portland, Oregon, United States, 97210
        • Isotechnika Investigational Site
      • Portland, Oregon, United States, 97239-2940
        • Isotechnika Investigational Site
      • Portland, Oregon, United States, 97329-2940
        • Isotechnika Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Isotechnika Investigational Site
      • Philadelphia, Pennsylvania, United States, 19104
        • Isotechnika Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Isotechnika Investigational Site
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Isotechnika Investigational Site
    • Texas
      • Dallas, Texas, United States, 75246
        • Isotechnika Investigational Site
      • Houston, Texas, United States, 77030
        • Isotechnika Investigational Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Isotechnika Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • ISA247
Active Comparator: Mid Dose Voclosporin
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Names:
  • ISA247
Active Comparator: High Dose Voclosporin
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Names:
  • ISA247
Active Comparator: Tacrolimus
Standard Dose Tacrolimus
Drug: tacrolimus
tacrolimus 0.05 mg/kg po BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Six months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Six months
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.
Six months
Patient Survival
Time Frame: Six months
Six months
Graft Survival
Time Frame: Six months
Six months
Hypertension, Hyperlipidemia, or Hyperglycemia
Time Frame: Six months
Six months
A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up.
Time Frame: Six months
Six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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
  • Study Director: Mark Pescovitz, MD, Indiana University
  • Study Director: A. Osama Gaber, MD, The Methodist Hospital Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

December 23, 2005

First Submitted That Met QC Criteria

December 23, 2005

First Posted (Estimate)

December 28, 2005

Study Record Updates

Last Update Posted (Estimate)

February 12, 2013

Last Update Submitted That Met QC Criteria

February 11, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISA05-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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