BK Virus Infection Clinical Trial
Official title:
Safety and Efficacy of Mycophenolic Acid Withdrawal With Conversion to Zortress (Everolimus) in Renal Transplant Recipients With BK Virus Infection
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.
Status | Completed |
Enrollment | 40 |
Est. completion date | November 2015 |
Est. primary completion date | February 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
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 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 ALT, 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 eGFR < 40 ml/min - Patients who have undergone desensitization |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of California, San Francisco | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
University of California, San Francisco |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Evidence of reduction of BK viruria and/or clearance of BK viremia | The primary objective of this pilot study is to evaluate whether concentration-controlled Zortress (everolimus) is superior to mycophenolic acid (MPA) on a composite endpoint of >50% reduction of BK viruria and/or clearance of BK viremia at 3-months post-randomization in maintenance renal transplant recipients. | 3 months post-randomization | No |
Secondary | Evaluation for the development of BK virus nephropathy or doubling of BK viremia levels | A doubling of BK viremia levels or the development of BKV nephropathy in subjects enrolled in the experimental study arm will prompt a conversion to standard care therapy. We will closely monitor BKV levels in the urine and blood and assess renal function monthly, as per our usual standard of care. Based on BKV results as well as renal function, as assessed by serum Cr, biopsies may be done for cause. Patients will have a final visit at month 4 to monitor for adverse events. | Month 1 - Month 4 | Yes |
Secondary | Correlation of p70S6 kinase phosphorylation inhibition with BKV replication and correlation of immune monitoring tests with rejection episodes based on BKV infection treatment regimen | We will investigate the correlation between inhibition of p70S6 kinase phosphorylation and BKV replication. Measurement of p70S6 kinase activity has also been used as a biomarker to predict rejection episodes. A whole blood assay based on the measurement of the expression of three NFAT-regulated genes IL-2, interferon gamma, and GM-CSF, has been developed to predict and monitor the biologic effects of calcineurin-based immunosuppression. The level of expression of these genes is correlated with rejections, recurrent infections, and malignancies in patients maintained on CNIs. | Month 1 - Month 4 | No |
Secondary | Evaluation for the development of proteinuria and hyperlipidemia | Patients will be monitored for the development of proteinuria and hyperlipidemia, a known side effect of everolimus treatment. An interim analysis will be performed once 50% of subjects have completed the study protocol and patients will have a final visit at month 4 to monitor for adverse events. | Month 1 - Month 4 | Yes |
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