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.

Study Overview

• Status: Terminated
• Conditions: Viremia; Viruria
• Intervention / Treatment: Drug: Leflunomide and orotic acid

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois, Chicago
    • Chicago, Illinois, United States, 60612
      • Rush Univeristy
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Transplant Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Lousiville
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Patients receive standard of care.
Experimental: Treatment Group; Dose adjusted leflunomide plus 600 mg orotic acid.	Drug: Leflunomide and orotic acid; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Changzheng-Cinkate
• Investigators: Principal Investigator: James W Williams, MD, Cinkate Corp

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: June 13, 2012
• First Submitted That Met QC Criteria: June 14, 2012
• First Posted (Estimate): June 15, 2012

Study Record Updates

• Last Update Posted (Actual): December 5, 2018
• Last Update Submitted That Met QC Criteria: December 3, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Renal Allograft Rejection; leflunomide; orotic acid; Polyoma BK Viruria; Polyoma BK Viremia; Polyoma BK Nephropathy
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Leflunomide
• Other Study ID Numbers: CK2012-001