NCT01620268

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_2

Geographic Reach
1 country

9 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 13, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 15, 2012

Completed
16 days until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

December 5, 2018

Status Verified

December 1, 2018

Enrollment Period

5.9 years

First QC Date

June 13, 2012

Last Update Submit

December 3, 2018

Conditions

Keywords

leflunomideorotic acidPolyoma BK ViruriaPolyoma BK ViremiaPolyoma BK NephropathyRenal Allograft Rejection

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Absence of viremia

    12 weeks

  • Absence of Polyoma BK Nephropathy

    12 weeks

  • No rejection of the renal allograft

    12 weeks

Study Arms (2)

Control Group

NO INTERVENTION

Patients receive standard of care.

Treatment Group

EXPERIMENTAL

Dose adjusted leflunomide plus 600 mg orotic acid.

Drug: Leflunomide and orotic acid

Interventions

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

Treatment Group

Eligibility Criteria

AgeUp to 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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),
  • Serum creatinine \<2.0 mg/dL
  • Hct \> 30%
  • WBC \> 3,500 x 103/L
  • Platelet count \> 150,000 x 103/L
  • Normal values for ALT, AST and bilirubin; Alk Phos \< 2 X upper limits of normal
  • No symptomatic cardiac, pulmonary, GI, hepatic or neurologic disease
  • No other active infections
  • Receiving CyA or Tacrolimus, Mycophenolate/Azathioprine + prednisone.
  • Is not pregnant as verified by a pregnancy test

You may not qualify if:

  • Is not able to comply with study procedures and dosing.
  • Has psychiatric instability.
  • 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),
  • Has a cancer diagnosis within past five years with potential for recurrence.
  • Has received experimental drug within past 3 months.
  • Is receiving immune suppressive drug other than those listed above calcineurin inhibitor, mycophenolate/azathioprine and +/- corticosteroid)
  • 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.
  • Has any neurologic abnormalities including peripheral neuropathy.
  • Is receiving concomitant therapy with drug known to have hepatotoxic risk.
  • Has known or suspected liver disease or current alcohol abuse.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Rush Univeristy

Chicago, Illinois, 60612, United States

Location

University of Illinois, Chicago

Chicago, Illinois, 60612, United States

Location

The University of Chicago Transplant Center

Chicago, Illinois, 60637, United States

Location

IU Health

Indianapolis, Indiana, 46202, United States

Location

University of Lousiville

Louisville, Kentucky, 40202, United States

Location

Beth Israel Deaconess Hospital

Boston, Massachusetts, 02215, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

MeSH Terms

Conditions

Viremia

Interventions

LeflunomideOrotic Acid

Condition Hierarchy (Ancestors)

Virus DiseasesInfectionsSepsisSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

IsoxazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAcids, HeterocyclicUracilPyrimidinonesPyrimidines

Study Officials

  • James W Williams, MD

    Cinkate Corp

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 13, 2012

First Posted

June 15, 2012

Study Start

July 1, 2012

Primary Completion

June 1, 2018

Study Completion

June 1, 2018

Last Updated

December 5, 2018

Record last verified: 2018-12

Locations