Study of ISA247 (Voclosporin) in De Novo Renal Transplantation

Kidney Diseases Clinical Trial

— PROMISE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00270634
• Other study ID #: ISA05-01
• Status: Completed
• Phase: Phase 2
• First received: December 23, 2005
• Last updated: February 11, 2013
• Start date: January 2006
• Est. completion date: July 2009

Study information

• Verified date: February 2013
• Source: Aurinia Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Diseases

Intervention

Drug:
• Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
• tacrolimus
tacrolimus 0.05 mg/kg po BID

Locations

Country	Name	City	State
Canada	Isotechnika Investigational Site	Edmonton	Alberta
Canada	Isotechnika Investigational Site	London	Ontario
Canada	Isotechnika Investigational Site	Montreal	Quebec
Canada	Isotechnika Investigational Site	Saskatoon	Saskatchewan
Canada	Isotechnika Investigational Site	Toronto	Ontario
United States	Isotechnika Investigational Site	Ann Arbor	Michigan
United States	Isotechnika Investigational Site	Baltimore	Maryland
United States	Isotechnika Investigational Site	Birmingham	Alabama
United States	Isotechnika Investigational Site	Boston	Massachusetts
United States	Isotechnika Investigational Site	Buffalo	New York
United States	Isotechnika Investigational Site	Charleston	South Carolina
United States	Isotechnika Investigational Site	Chicago	Illinois
United States	Isotechnika Investigational Site	Chicago	Illinois
United States	Isotechnika Investigational Site	Cincinnati	Ohio
United States	Isotechnika Investigational Site	Cincinnati	Ohio
United States	Isotechnika Investigational Site	Dallas	Texas
United States	Isotechnika Investigational Site	Denver	Colorado
United States	Isotechnika Investigational Site	Detroit	Michigan
United States	Isotechnika Investigational Site	Durham	North Carolina
United States	Isotechnika Investigational Site	Gainesville	Florida
United States	Isotechnika Investigational Site	Hawthorne	New York
United States	Isotechnika Investigational Site	Houston	Texas
United States	Isotechnika Investigational Site	Lexington	Kentucky
United States	Isotechnika Investigational Site	Livingston	New Jersey
United States	Isotechnika Investigational Site	Los Angeles	California
United States	Isotechnika Investigational Site	Los Angeles	California
United States	Isotechnika Investigational Site	Los Angeles	California
United States	Isotechnika Investigational Site	Memphis	Tennessee
United States	Isotechnika Investigational Site	New Orleans	Louisiana
United States	Isotechnika Investigational Site	New Orleans	Louisiana
United States	Isotechnika Investigational Site	New York	New York
United States	Isotechnika Investigational Site	Orange	California
United States	Isotechnika Investigational Site	Palo Alto	California
United States	Isotechnika Investigational Site	Philadelphia	Pennsylvania
United States	Isotechnika Investigational Site	Philadelphia	Pennsylvania
United States	Isotechnika Investigational Site	Portland	Oregon
United States	Isotechnika Investigational Site	Portland	Oregon
United States	Isotechnika Investigational Site	Portland	Oregon
United States	Isotechnika Investigational Site	Richmond	Virginia
United States	Isotechnika Investigational Site	Rochester	New York
United States	Isotechnika Investigational Site	Rochester	Minnesota
United States	Isotechnika Investigational Site	San Diego	California
United States	Isotechnika Investigational Site	San Francisco	California
United States	Isotechnika Investigational Site	Tampa	Florida
United States	Isotechnika Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Aurinia Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biopsy Proven Acute Rejection (BPAR)	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	No
Secondary	To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR)	ANOVAs to test for differences in GFR at Month 6.	Six months	Yes
Secondary	The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition	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	No
Secondary	Patient Survival		Six months	Yes
Secondary	Graft Survival		Six months	Yes
Secondary	Hypertension, Hyperlipidemia, or Hyperglycemia		Six months	Yes
Secondary	A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up.		Six months	Yes