Safety and Efficacy Study of Everolimus to Treat BK Virus Infection in Kidney Transplant Recipients
Condition: BK Virus Infection
MeSH terms: Infections; Communicable Diseases; Virus Diseases
Intervention: Everolimus; Mycophenolic acid dose reduction
Intervention description: Everolimus will be administered orally at a starting dose of 0.75 mg PO b.i.d. (1.5 mg/day). Everolimus whole blood trough levels will be monitored at pre-specified time points to achieve a range of 3-8 ng/mL. Group 1 patients will continue on prednisone and tacrolimus with a target whole blood trough level of 3-6 ng/mL.; Group 2 patients will undergo a 50% reduction of the mycophenolic acid (MPA) dose, and continue with tacrolimus (target trough level of 6-10 ng/mL), and prednisone.
Intervention MeSH terms: Mycophenolic Acid; Everolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: BK virus; Kidney Transplantation; Immunologic Monitoring

Summary:

      This study is examining the safety and efficacy of converting anti-rejection therapy from
      mycophenolic acid (MPA) to Zortress (everolimus) in renal transplant recipients with BK virus
      infection.

      The study will also determine if immune monitoring tests can detect an association between BK
      virus infection and transplant rejection episodes, based on the specific BKV infection
      treatment regimen.

      The investigators hypothesize that an anti-rejection regimen with Zortress (everolimus) and
      tacrolimus + prednisone will be superior to a standard regimen of reduced dose MPA and
      tacrolimus + prednisone in patients who have undergone renal transplantation and have active
      BKV infections.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female renal transplant recipients 18-75 years of age (primary or
             re-transplant)

          -  Recipients of cadaveric, living unrelated or living related donor kidney

          -  Baseline immunosuppression (IS) consisting of tacrolimus, MPA, and prednisone

          -  Patients with BK viruria ≥ 1 million copies/mL and/or viremia (> 500 copies/mL) found
             on routine BKV screening.

          -  Patients who have given written informed consent to participate in the study

        Exclusion Criteria:

          -  Patients who are ABO incompatible transplants

          -  Patients with an abnormal liver profile such as Alanine Aminotransferase (ALT),
             aspartate aminotransferase (AST), alkaline phosphatase, or total bilirubin > 3x ULN at
             the time of randomization

          -  Patients with severe total hypercholesterolemia (> 350 mg/dL) or total
             hypertriglyceridemia (> 500 mg/dL). Patients on lipid lowering drugs with controlled
             hyperlipidemia are acceptable.

          -  Patients with a platelet count < 100,000/mm3 at randomization

          -  Patients with an ANC < 1,500/mm3 or WBC < 4.5mm3

          -  Patients with a known hypersensitivity to the study drug or to drugs of similar
             chemical classes.

          -  Patients being treated with drugs (other than tacrolimus) that are potent inducers or
             inhibitors of cytochrome P4503A4

          -  Patients who have any surgical or medical condition, such as severe diarrhea, active
             peptic ulcer disease, or uncontrolled DM, which, in the opinion of the investigators,
             might significantly alter the absorption, distribution, metabolism and/or excretion of
             study medication.

          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive urine human chorionic gonadotrophin laboratory test

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, including women whose career, lifestyle, or sexual orientation
             precludes intercourse with a male partner and women whose partners have been
             sterilized by vasectomy or other means, UNLESS they are using two birth control
             methods. The two methods can be a double barrier method or a barrier method plus a
             hormonal method.

          -  Adequate barrier methods of contraception include: diaphragm, condom (by the partner),
             intrauterine device (copper or hormonal), sponge or spermicide. Hormonal
             contraceptives include any marketed contraceptive agent that includes an estrogen
             and/or a progestational agent.

          -  Reliable contraception should be maintained throughout the study and for 7 days after
             study drug discontinuation.

          -  Women are considered post-menopausal and not of child bearing potential if they have
             had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
             (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous
             amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had
             surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago.
             In the case of oophorectomy alone, only when the reproductive status of the woman has
             been confirmed by follow up hormone level assessment is she considered not of child
             bearing potential.

          -  Patients with baseline urine protein excretion > 500mg/day

          -  Patients with Estimated Glomerular Filtration Rate (eGFR) < 40 ml/min

          -  Patients who have undergone desensitization