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

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ClinicalTrials.gov Identifier: NCT00270634

Recruitment Status : Completed

First Posted : December 28, 2005

Results First Posted : February 12, 2013

Last Update Posted : February 12, 2013

Sponsor:

Information provided by (Responsible Party):

Aurinia Pharmaceuticals Inc.

Study Description

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 Design


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

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Tacrolimus

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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 :

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
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

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 ClinicalTrials.gov identifier (NCT number): NCT00270634

Hide Study Locations

Locations


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

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 of Results:

Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.

Other Publications:

Gregory CR, Kyles AE, Bernsteen L, Wagner GS, Tarantal AF, Christe KL, Brignolo L, Spinner A, Griffey SM, Paniagua RT, Hubble RW, Borie DC, Morris RE. Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation. 2004 Sep 15;78(5):681-5.

Stalder M, Bîrsan T, Hubble RW, Paniagua RT, Morris RE. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant. 2003 Dec;22(12):1343-52.

Abel MD, Aspeslet LJ, Freitag DG, Naicker S, Trepanier DJ, Kneteman NM, Foster RT, Yatscoff RW. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant. 2001 Feb;20(2):161.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mayo PR, Ling SY, Huizinga RB, Freitag DG, Aspeslet LJ, Foster RT. Population PKPD of voclosporin in renal allograft patients. J Clin Pharmacol. 2014 May;54(5):537-45. doi: 10.1002/jcph.237. Epub 2013 Nov 30.


Responsible Party:	Aurinia Pharmaceuticals Inc.
ClinicalTrials.gov 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 Immunosuppression Adult Kidney Transplantation Treatment Outcome

Additional relevant MeSH terms:


Kidney Diseases Urologic Diseases Tacrolimus Cyclosporine 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

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