Study of ISA247 (Voclosporin) in De Novo Renal Transplantation

NCT ID: NCT00270634

Last Updated: 2013-02-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

334 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-01-31

Study Completion Date

2009-07-31

Brief Summary

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

Detailed Description

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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

Conditions

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Kidney Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low Dose Voclosporin

Low dose voclosporin

Group Type ACTIVE_COMPARATOR

Voclosporin

Intervention Type DRUG

voclosporin 0.4, 0.6, 0.8 mg/kg po BID

Mid Dose Voclosporin

Mid Dose Voclosporin

Group Type ACTIVE_COMPARATOR

Voclosporin

Intervention Type DRUG

voclosporin 0.4, 0.6, 0.8 mg/kg po BID

High Dose Voclosporin

High Dose Voclosporin

Group Type ACTIVE_COMPARATOR

Voclosporin

Intervention Type DRUG

voclosporin 0.4, 0.6, 0.8 mg/kg po BID

Tacrolimus

Standard Dose Tacrolimus

Group Type ACTIVE_COMPARATOR

tacrolimus

Intervention Type DRUG

tacrolimus 0.05 mg/kg po BID

Interventions

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Voclosporin

voclosporin 0.4, 0.6, 0.8 mg/kg po BID

Intervention Type DRUG

tacrolimus

tacrolimus 0.05 mg/kg po BID

Intervention Type DRUG

Other Intervention Names

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ISA247

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aurinia Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Abramowicz, MD, PhD

Role: STUDY_DIRECTOR

Erasme hospital

Philip Belitsky, MD

Role: STUDY_DIRECTOR

No Affiliation

Arthur Matas, MD

Role: STUDY_DIRECTOR

University of Minnesota

Mark Pescovitz, MD

Role: STUDY_DIRECTOR

Indiana University

A. Osama Gaber, MD

Role: STUDY_DIRECTOR

The Methodist Hospital Research Institute

Locations

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Isotechnika Investigational Site

Birmingham, Alabama, United States

Site Status

Isotechnika Investigational Site

Los Angeles, California, United States

Site Status

Isotechnika Investigational Site

Los Angeles, California, United States

Site Status

Isotechnika Investigational Site

Los Angeles, California, United States

Site Status

Isotechnika Investigational Site

Orange, California, United States

Site Status

Isotechnika Investigational Site

Palo Alto, California, United States

Site Status

Isotechnika Investigational Site

San Diego, California, United States

Site Status

Isotechnika Investigational Site

San Francisco, California, United States

Site Status

Isotechnika Investigational Site

Denver, Colorado, United States

Site Status

Isotechnika Investigational Site

Gainesville, Florida, United States

Site Status

Isotechnika Investigational Site

Tampa, Florida, United States

Site Status

Isotechnika Investigational Site

Chicago, Illinois, United States

Site Status

Isotechnika Investigational Site

Chicago, Illinois, United States

Site Status

Isotechnika Investigational Site

Lexington, Kentucky, United States

Site Status

Isotechnika Investigational Site

New Orleans, Louisiana, United States

Site Status

Isotechnika Investigational Site

New Orleans, Louisiana, United States

Site Status

Isotechnika Investigational Site

Baltimore, Maryland, United States

Site Status

Isotechnika Investigational Site

Boston, Massachusetts, United States

Site Status

Isotechnika Investigational Site

Ann Arbor, Michigan, United States

Site Status

Isotechnika Investigational Site

Detroit, Michigan, United States

Site Status

Isotechnika Investigational Site

Rochester, Minnesota, United States

Site Status

Isotechnika Investigational Site

Livingston, New Jersey, United States

Site Status

Isotechnika Investigational Site

Buffalo, New York, United States

Site Status

Isotechnika Investigational Site

Hawthorne, New York, United States

Site Status

Isotechnika Investigational Site

New York, New York, United States

Site Status

Isotechnika Investigational Site

Rochester, New York, United States

Site Status

Isotechnika Investigational Site

Durham, North Carolina, United States

Site Status

Isotechnika Investigational Site

Winston-Salem, North Carolina, United States

Site Status

Isotechnika Investigational Site

Cincinnati, Ohio, United States

Site Status

Isotechnika Investigational Site

Cincinnati, Ohio, United States

Site Status

Isotechnika Investigational Site

Portland, Oregon, United States

Site Status

Isotechnika Investigational Site

Portland, Oregon, United States

Site Status

Isotechnika Investigational Site

Portland, Oregon, United States

Site Status

Isotechnika Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Isotechnika Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Isotechnika Investigational Site

Charleston, South Carolina, United States

Site Status

Isotechnika Investigational Site

Memphis, Tennessee, United States

Site Status

Isotechnika Investigational Site

Dallas, Texas, United States

Site Status

Isotechnika Investigational Site

Houston, Texas, United States

Site Status

Isotechnika Investigational Site

Richmond, Virginia, United States

Site Status

Isotechnika Investigational Site

Edmonton, Alberta, Canada

Site Status

Isotechnika Investigational Site

London, Ontario, Canada

Site Status

Isotechnika Investigational Site

Toronto, Ontario, Canada

Site Status

Isotechnika Investigational Site

Montreal, Quebec, Canada

Site Status

Isotechnika Investigational Site

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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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. doi: 10.1097/01.tp.0000131950.75697.71.

Reference Type BACKGROUND
PMID: 15371668 (View on PubMed)

Stalder M, Birsan 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. doi: 10.1016/s1053-2498(03)00033-0.

Reference Type BACKGROUND
PMID: 14672749 (View on PubMed)

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. doi: 10.1016/s1053-2498(00)00290-4. No abstract available.

Reference Type BACKGROUND
PMID: 11250240 (View on PubMed)

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.

Reference Type RESULT
PMID: 21943027 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24243422 (View on PubMed)

Other Identifiers

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ISA05-01

Identifier Type: -

Identifier Source: org_study_id

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