This is a randomized, double-blind, placebo-controlled, sequential dose escalation study to assess the safety, tolerability and preliminary effectiveness of cidofovir (VISTIDE�) in kidney transplant patients who have been diagnosed BK virus nephopathy (BKVN). Up to 48 adult male and female allograft recipients of any race with biopsy-confirmed BK virus nephropathy may be enrolled sequentially into one or f 3 dose levels (0.25, 0.5 and 1.0 mg/kg) of cidofovir to identify the maximum tolerated dose among the 3 dose levels. To assess potential effectiveness of the treatment, his study will also evaluate the antiviral effect of each 3 dose level, evaluate the pharmacokinetics/pharmacodynamics of cidofovir in these patients, and evaluate the impact of treatment of allograft function and allograft rejection at the completion of the study.

Condition	Intervention	Phase
BK virus (nephropathy)	Vaccine: Cidofovir (VISTIDE)	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  48

This is a phase I/II, randomized, double-blind, placebo-controlled, sequential dose escalation study of a marketed product cidofovir (VISTIDE�) administered intravenously to renal allograft recipients who have been newly diagnosed with BK virus nephropathy (BKVN). Approximately 48 adult male and female renal allograft recipients of any race with biopsy-confirmed BK virus nephropathy will randomized in sequential cohorts to evaluate the safety and tolerability of 3 dose levels (0.25, 0.5 and 1.0 mg/kg) and to identify the maximum tolerated dose among the 3 dose levels. To evaluate the potential effectiveness of cidofovir treatment in this patient population, study will also assess the antiviral effect of each 3 dose levels, and evaluate the pharmacokinetics/pharmacodynamics of cidofovir in these patients. Allograft function and allograft rejection will also be assessed at the completion of the study. Seroepidemiologic studies have demonstrated that BK virus infection is almost universal and occurs in early childhood. BK virus rarely reactivates in immunocompetent adults, however; symptomatic infections and clinical disease can occur in immunosuppressed kidney transplant recipients. The more serious clinical manifestations include ureteral stenosis and kidney infection (BKVN). The current approach to patients with BKVN is to reduce immunosupressive regimen, however despite reduction in immunosuppression, 30-70% still manifest progressive deterioration in renal function and poor allograft outcome which eventually results in allograft loss. Preclinical data suggest an antiviral effect of cidofovir against BK virus. Published and anecdotal clinical data suggest benefit of this treatment to patients, however, no controlled studies have been conducted to formally establish the safety and effectiveness of treatment. This study will establish whether cidofovir is safe and well- tolerated in patients with BKVN and will provide important background safety and effectiveness data for the design of pivotal efficacy studies.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Age 18 years or older
2. Kidney or kidney/pancreas transplant recipient
3. New onset BKVN diagnosed by an allograft renal biopsy demonstrating BK virus inclusion and confirmed by immunohistochemistry, electron microscopy and/or in situ hybridization (biopsy must have been obtained within 21 days prior to receipt of study drug and must have been conducted as part of patient standard of care)
4. PCR BK virus load in plasma >10,000 copies/mL (confirmed at the CASG Virology Laboratory)
5. Glomerular filtration rate >30mL/min using Levey calculations
6. Absolute neutrophil count >1000/�l (with GCSF support as necessary)
7. Women must be post menopausal, surgically sterile or willing to use adequate contraception (barrier method with spermicide, IUD, oral contraceptivew, implant or other licensed hormone method) from time of study enrollment through 3 months post last dose of study treatment.Men must be surgically sterile or willing to use contraception (barrier method with spermicide) from time of study enrollment through 3 months post last dose of study treatment.

Exclusion Criteria:

1. Unable to obtain valid informed consent 2. History of intolerance to cidofovir or related compounds (i.e. other nucleotide derivatives [adefovir or tenofovir]) 3. Pregnant or breast feeding women 4. Prior treatment with cidofovir within the last 2 weeks 5. Receipt of another investigational drug with proven nephrotoxic drug interaction with cidofovir or known antipolyoma virus activity one month prior to study entry 6. Contraindication to renal biopsy (e.g. anticoagulant medication, unwilling to undergo biopsy) 7. Currently receiving or anticipated to receive any of the following within 2 weeks of randomization:

a. Amphotericin preparation b. Aminoglycosides c. Platinum-based chemotherapeutic agents d. NSAIDS-non steroidal anti-inflammatory drugs e. Foscarnet f. IV Pentamidine g. Probenecid h. Leflunomide 8. Known ocular disease (hypotony or uveitis)

Please refer to this study by ClinicalTrials.gov identifier  NCT00138424

Richard Whitley      (205) 934-5316 

Alabama
      University of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      University of California at San Francisco, San Francisco,  California,  94143-0124,  United States
Colorado
      University of Colorado Health Sciences Center, Denver,  Colorado,  80262,  United States
Illinois
      University of Chicago, Chicago,  Illinois,  60637,  United States
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States
      University of Minnesota, Minneapolis,  Minnesota,  55455,  United States
New Hampshire
      Dartmouth Hitchcock Medical Center, Lebanon,  New Hampshire,  03756,  United States
Washington
      University of Washington, Seattle,  Washington,  98195-7110,  United States
      University of Washington Medical Center, Seattle,  Washington,  98195-7110,  United States
      University of Washington Medical Center, Seattle,  Washington,  98195-7110,  United States
Wisconsin
      University of Wisconsin Medical School, Madison,  Wisconsin,  53792,  United States

Study ID Numbers:  04-047; CASG 209
Last Updated:  August 29, 2005
Record first received:  August 26, 2005
ClinicalTrials.gov Identifier:  NCT00138424
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-30