Study of ISA247 (Voclosporin) in De Novo Renal Transplantation

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

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.