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

Phase 2

Terminated

• Conditions: Viruria; Viremia
• Interventions: Drug: Leflunomide and orotic acid

• Registration Number: NCT01620268
• Lead Sponsor: Changzheng-Cinkate

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 Timeline

• Study First Submitted: 2012-06-13
• Study First Submitted QC: 2012-06-14
• Study First Posted: 2012-06-15
• Study Start: 2012-07
• Primary Completion: 2018-06
• Study Completion: 2018-06
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-03
• Last Update Posted: 2018-12-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Leflunomide and orotic acid	Dose adjusted leflunomide plus 600 mg orotic acid.

Primary Outcome Measures

Name	Time	Method
Clearance of viruria	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 Outcome Measures

Name	Time	Method
Absence of viremia	12 weeks	No more that 1000 copies of Polyoma BK Virus in the blood on two consecutive tests 2 weeks or more apart
Absence of Polyoma BK Nephropathy	12 weeks	Absence of Polyoma BK Nephropathy
No rejection of the renal allograft	12 weeks	No rejection of the renal allograft

Trial Locations

Locations (9)

IU Health; 🇺🇸 Indianapolis, Indiana, United States

University of Lousiville; 🇺🇸 Louisville, Kentucky, United States

Beth Israel Deaconess Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Alabama, Birmingham; 🇺🇸 Birmingham, Alabama, United States

Rush Univeristy; 🇺🇸 Chicago, Illinois, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

University of Illinois, Chicago; 🇺🇸 Chicago, Illinois, United States

The University of Chicago Transplant Center; 🇺🇸 Chicago, Illinois, United States

Methodist University Hospital; 🇺🇸 Memphis, Tennessee, United States