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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Viruria, Viremia

Intervention / Treatment
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* Drug: Leflunomide and orotic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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), Serum creatinine <2.0 mg/dL Hct > 30% WBC > 3,500 x 103/L Platelet count > 150,000 x 103/L Normal values for ALT, AST and bilirubin; Alk Phos < 2 X upper limits of normal No symptomatic cardiac, pulmonary, GI, hepatic or neurologic disease No other active infections Receiving CyA or Tacrolimus, Mycophenolate/Azathioprine + prednisone. Is not pregnant as verified by a pregnancy test Exclusion Criteria: Is not able to comply with study procedures and dosing. Has psychiatric instability. 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. 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), Has a cancer diagnosis within past five years with potential for recurrence. Has received experimental drug within past 3 months. Is receiving immune suppressive drug other than those listed above calcineurin inhibitor, mycophenolate/azathioprine and +/- corticosteroid) 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. Has any neurologic abnormalities including peripheral neuropathy. Is receiving concomitant therapy with drug known to have hepatotoxic risk. Has known or suspected liver disease or current alcohol abuse.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>Patients receive standard of care. | |
| Experimental: Treatment Group<br>Dose adjusted leflunomide plus 600 mg orotic acid. | Drug: Leflunomide and orotic acid<br>* Daily dose of leflunomide adjusted to target steady state blood levels of 50 ug/mL to 100 ug/mL of the active metabolite plus 600 mg orotic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of viruria | Viral load of Polyoma BK virus in urine reduced from greater than or equal to 10 million copies/mL to less than 500,000 copies/mL or a 2 log reduction in copies/mL. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of viremia | No more that 1000 copies of Polyoma BK Virus in the blood on two consecutive tests 2 weeks or more apart | 12 weeks | 
| Absence of Polyoma BK Nephropathy | Absence of Polyoma BK Nephropathy | 12 weeks | 
| No rejection of the renal allograft | No rejection of the renal allograft | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leflunomide, orotic acid, Polyoma BK Viruria, Polyoma BK Viremia, Polyoma BK Nephropathy, Renal Allograft Rejection