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

This study is currently recruiting participants.
Verified September 2013 by Changzheng-Cinkate
Sponsor:
Information provided by (Responsible Party):
Changzheng-Cinkate
ClinicalTrials.gov Identifier:
NCT01620268
First received: June 13, 2012
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Viruria
Viremia
Drug: Leflunomide and orotic acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Changzheng-Cinkate:

Primary Outcome Measures:
  • Clearance of viruria [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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:
  • Absence of viremia [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Absence of Polyoma BK Nephropathy

  • No rejection of the renal allograft [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    No rejection of the renal allograft


Estimated Enrollment: 60
Study Start Date: July 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01620268

Contacts
Contact: James W. Williams, MD 7734263209 jameswarrenwilliams@msn.com
Contact: James L Yeager, PhD 8472839176 james_yeager@msn.com

Locations
United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Tina Ayer, BS,CCRP    205-996-2577    tayer@uab.edu   
Principal Investigator: Clifton Kew, MD         
United States, Florida
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Contact: Deborah Fernandez, RN    813-844-5692    debbiefernandez@tgh.org   
Principal Investigator: Rajendra Baliga, MD         
United States, Illinois
The University of Chicago Transplant Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Mark Lockwood, MSN, RN    773-834-0684    mlockwood@surgery.bsd.uchicago.edu   
Principal Investigator: Michelle Josephson, MD         
United States, Massachusetts
Beth Israel Deaconess Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susan M McDermott, RN, MPH    617-632-9841    smcderm2@bidmc.harvard.edu   
Principal Investigator: Didier A Mandelbrot, MD         
United States, Missouri
Washington University, St Louis Recruiting
St Louis, Missouri, United States, 63110
Contact: Rebecca Cusanelli, RN, MSN, CCTC    3143624109    rcusanel@DOM.wustl.edu   
Principal Investigator: Daniel Brennan, MD         
United States, Tennessee
Methodist University Hospital Recruiting
Memphis, Tennessee, United States, 38104
Contact: Oleksandra Dryn, MD    901-516-2031    oleksandra.dryn@mlh.org   
Principal Investigator: Vinaya Rao, MD         
Sponsors and Collaborators
Changzheng-Cinkate
  More Information

No publications provided

Responsible Party: Changzheng-Cinkate
ClinicalTrials.gov Identifier: NCT01620268     History of Changes
Other Study ID Numbers: CK2012-001
Study First Received: June 13, 2012
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Changzheng-Cinkate:
leflunomide
orotic acid
Polyoma BK Viruria
Polyoma BK Viremia
Polyoma BK Nephropathy
Renal Allograft Rejection

Additional relevant MeSH terms:
Viremia
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Leflunomide
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014