Clinical trial NCT00270634: Study of ISA247 (Voclosporin) in De Novo Renal Transplantation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Diseases
Keywords: Randomized Controlled Trials
Immunosuppression
Adult
Kidney Transplantation
Treatment Outcome
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2005-12-28
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Biopsy Proven Acute Rejection (BPAR)
timeFrame: Six months
Secondary outcomes:
measure: To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR)
timeFrame: Six months
measure: The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition
timeFrame: Six months
measure: Patient Survival
timeFrame: Six months
measure: Graft Survival
timeFrame: Six months
measure: Hypertension, Hyperlipidemia, or Hyperglycemia
timeFrame: Six months
measure: A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up.
timeFrame: Six months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Isotechnika Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: Isotechnika Investigational Site
state: California
city: Los Angeles
country: United States
facility: Isotechnika Investigational Site
state: California
city: Los Angeles
country: United States
facility: Isotechnika Investigational Site
state: California
city: Orange
country: United States
facility: Isotechnika Investigational Site
state: California
city: Palo Alto
country: United States
facility: Isotechnika Investigational Site
state: California
city: San Diego
country: United States
facility: Isotechnika Investigational Site
state: California
city: San Francisco
country: United States
facility: Isotechnika Investigational Site
state: California
city: Denver
country: United States
facility: Isotechnika Investigational Site
state: Colorado
city: Gainesville
country: United States
facility: Isotechnika Investigational Site
state: Florida
city: Tampa
country: United States
facility: Isotechnika Investigational Site
state: Florida
city: Chicago
country: United States
facility: Isotechnika Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Isotechnika Investigational Site
state: Illinois
city: Lexington
country: United States
facility: Isotechnika Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: Isotechnika Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: Isotechnika Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Isotechnika Investigational Site
state: Maryland
city: Boston
country: United States
facility: Isotechnika Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Isotechnika Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Isotechnika Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Isotechnika Investigational Site
state: Minnesota
city: Livingston
country: United States
facility: Isotechnika Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: Isotechnika Investigational Site
state: New York
city: Hawthorne
country: United States
facility: Isotechnika Investigational Site
state: New York
city: New York
country: United States
facility: Isotechnika Investigational Site
state: New York
city: Rochester
country: United States
facility: Isotechnika Investigational Site
state: New York
city: Durham
country: United States
facility: Isotechnika Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Isotechnika Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Isotechnika Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Isotechnika Investigational Site
state: Ohio
city: Portland
country: United States
facility: Isotechnika Investigational Site
state: Oregon
city: Portland
country: United States
facility: Isotechnika Investigational Site
state: Oregon
city: Portland
country: United States
facility: Isotechnika Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Isotechnika Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Isotechnika Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Isotechnika Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Isotechnika Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Isotechnika Investigational Site
state: Texas
city: Houston
country: United States
facility: Isotechnika Investigational Site
state: Texas
city: Richmond
country: United States
facility: Isotechnika Investigational Site
state: Virginia
city: Edmonton
country: Canada
facility: Isotechnika Investigational Site
state: Alberta
city: London
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: Isotechnika Investigational Site
state: Saskatchewan
Study officials:
affiliation: Erasme hospital
name: Daniel Abramowicz, MD, PhD
role: STUDY_DIRECTOR
affiliation: No Affiliation
name: Philip Belitsky, MD
role: STUDY_DIRECTOR
affiliation: University of Minnesota
name: Arthur Matas, MD
role: STUDY_DIRECTOR
affiliation: Indiana University
name: Mark Pescovitz, MD
role: STUDY_DIRECTOR
affiliation: The Methodist Hospital Research Institute
name: A. Osama Gaber, MD
role: STUDY_DIRECTOR
References:
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. doi: 10.1097/01.tp.0000131950.75697.71.
citation: 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.
citation: 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.
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. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.
citation: 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.