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
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 24
- Locations
- 9
- Primary Endpoint
- Clearance of viruria
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- — to 75 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Treatment Group
Dose adjusted leflunomide plus 600 mg orotic acid.
Intervention: Leflunomide and orotic acid (Drug)
Outcomes
Primary Outcomes
Clearance of viruria
Time Frame: 12 weeks
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.
Secondary Outcomes
- Absence of viremia(12 weeks)
- Absence of Polyoma BK Nephropathy(12 weeks)
- No rejection of the renal allograft(12 weeks)