An Open-Label, Study to Treat Patients With Renal Allograft and Polyoma BK Viruria

An Open-Label, Phase 2 Study to Treat Patients With Renal Allograft and Polyoma BK Viruria to Prevent Polyoma BK Viremia, Polyoma BK Nephropathy and Renal Allograft Rejection

This study will evaluate the clinical efficacy and safety of a combination of leflunomide and orotic acid in kidney transplant patients with high levels of Polyoma BK viruria for the purpose of preventing Polyoma BK viremia and Nephropathy that could lead to kidney transplant loss from viral damage, acute rejection or both.

This is a multicenter, randomized trial that will evaluate the effect of a combination of leflunomide and orotic acid for the treatment of Polyoma BK viruria. In this multicenter trial, renal allograft patients with the diagnosis of Polyoma BK viruria as determined by a viral level in the urine of 25 million or more copies/mL, and no detectable viremia, will complete a screening visit (V1) to determine eligibility for the study based on inclusion/exclusion criteria. Patients that meet the entrance criteria for this study will be randomly assigned to one of two treatment groups at Visit (2) and enter a 4 month dosing period.

Inclusion Criteria:

1. Patients, 75 years of age or less, with the diagnosis of renal allograft Polyoma BK viruria of 10 million or more copies/mL in their urine confirmed by PCR at the central laboratory.
2. No viremia (viremia is defined as greater than 1,000 copies/ml plasma on two consecutive tests two weeks or more apart as measured at the designated central laboratory),
3. Serum creatinine <2.0 mg/dL
4. Hct > 30%
5. WBC > 3,500 x 103/L
6. Platelet count > 150,000 x 103/L
7. Normal values for ALT, AST and bilirubin; Alk Phos < 2 X upper limits of normal
8. No symptomatic cardiac, pulmonary, GI, hepatic or neurologic disease
9. No other active infections
10. Receiving CyA or Tacrolimus, Mycophenolate/Azathioprine + prednisone.
11. Is not pregnant as verified by a pregnancy test

Exclusion Criteria:

1. Is not able to comply with study procedures and dosing.
2. Has psychiatric instability.
3. Has an active systemic infection including Hepatitis B or C, HIV, or on anti-viral therapy within seven days of entering the study. Note however, that the subjects may be taking ganciclovir, valaciclovir, acyclovir and valganciclovir and therefore these are not exclusionary antiviral medications.
4. Has BK viremia (viremia is defined as greater than 1,000 copies/ml plasma on two consecutive tests two weeks or more apart as measured at the designated central laboratory), or has had a single episode of BK viremia. (viremia is defined as greater than 1,000 copies/ml plasma on two consecutive tests two weeks or more apart as measured at the designated central laboratory or the local laboratory),
5. Has a cancer diagnosis within past five years with potential for recurrence.
6. Has received experimental drug within past 3 months.
7. Is receiving immune suppressive drug other than those listed above calcineurin inhibitor, mycophenolate/azathioprine and +/- corticosteroid)
8. Is a woman of child bearing potential or is a male with female partner of child bearing potential who is unwilling to use reliable contraception.
9. Has any neurologic abnormalities including peripheral neuropathy.
10. Is receiving concomitant therapy with drug known to have hepatotoxic risk.
11. Has known or suspected liver disease or current alcohol abuse.