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

Viremia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01620268
• Other study ID #: CK2012-001
• Status: Terminated
• Phase: Phase 2
• Start date: July 2012
• Est. completion date: June 2018

Study information

• Verified date: December 2018
• Source: Changzheng-Cinkate
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Viremia
• Viruria

Intervention

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

Locations

Country	Name	City	State
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Hospital	Boston	Massachusetts
United States	Rush Univeristy	Chicago	Illinois
United States	The University of Chicago Transplant Center	Chicago	Illinois
United States	University of Illinois, Chicago	Chicago	Illinois
United States	IU Health	Indianapolis	Indiana
United States	University of Lousiville	Louisville	Kentucky
United States	Methodist University Hospital	Memphis	Tennessee
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Changzheng-Cinkate

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Absence of Polyoma BK Nephropathy	Absence of Polyoma BK Nephropathy	12 weeks
Secondary	No rejection of the renal allograft	No rejection of the renal allograft	12 weeks