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

• ClinicalTrials.gov Identifier: NCT01620268
• Recruitment Status: Terminated
• First Posted: June 15, 2012
• Last Update Posted: December 5, 2018
• Sponsor: Changzheng-Cinkate
• Information provided by (Responsible Party): Changzheng-Cinkate

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Viruria; Viremia	Drug: Leflunomide and orotic acid	Phase 2

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 (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: June 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Absence of viremia [ Time Frame: 12 weeks ]
   No more that 1000 copies of Polyoma BK Virus in the blood on two consecutive tests 2 weeks or more apart
2. Absence of Polyoma BK Nephropathy [ Time Frame: 12 weeks ]
   Absence of Polyoma BK Nephropathy
3. No rejection of the renal allograft [ Time Frame: 12 weeks ]
   No rejection of the renal allograft

Eligibility Criteria

• Ages Eligible for Study: up to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Alabama

University of Alabama, Birmingham

Birmingham, Alabama, United States, 35294

United States, Florida

Tampa General Hospital

Tampa, Florida, United States, 33606

United States, Illinois

Rush Univeristy

Chicago, Illinois, United States, 60612

University of Illinois, Chicago

Chicago, Illinois, United States, 60612

The University of Chicago Transplant Center

Chicago, Illinois, United States, 60637

United States, Indiana

IU Health

Indianapolis, Indiana, United States, 46202

United States, Kentucky

University of Lousiville

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Beth Israel Deaconess Hospital

Boston, Massachusetts, United States, 02215

United States, Tennessee

Methodist University Hospital

Memphis, Tennessee, United States, 38104

Sponsors and Collaborators

Changzheng-Cinkate

Investigators

• Principal Investigator: James W Williams, MD; Cinkate Corp

More Information

• Responsible Party: Changzheng-Cinkate
• ClinicalTrials.gov Identifier: NCT01620268
• Other Study ID Numbers: CK2012-001
• First Posted: June 15, 2012
• Last Update Posted: December 5, 2018
• Last Verified: December 2018

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; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Leflunomide; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs