Safety and Efficacy Study of Everolimus to Treat BK Virus Infection in Kidney Transplant Recipients

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

Status Completed

Clinical Trial 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.

Clinical Trial Description

This is a pilot study designed as a single center, randomized, open-label trial study comparing the safety and efficacy of MPA discontinuation with the addition of Zortress (everolimus) versus standard immunosuppression reduction in adult patients who have undergone a renal transplant and who have evidence of BKV infection. All kidney transplant recipients at UCSF are screened for BKV in the urine and plasma at months 1, 3, 6, 9, and 12 post-transplantation. The presence of viruria > 1 million copies/mL and/or viremia prompts a 50% reduction in the MPA dose as well as monthly monitoring of BKV in the urine and plasma. Renal transplant patients found to have BK viruria > 1 million copies/mL and/or viremia > 500 copies/mL on any screening lab will be eligible for enrollment.

Before any study-related evaluations are performed, the patient must give written informed consent. Once consent is obtained, patients will be randomized in consecutive blocks of 10, such that there will be 5 patients allocated to each group for each block. Only the study coordinator will have access to the block sequences. Patients will be randomized to one of two groups: group 1 will undergo MPA discontinuation with the addition of Zortress (everolimus) to their current regimen of tacrolimus and prednisone; group 2 will undergo a 50% dose reduction in MPA and continue with tacrolimus and prednisone.

The two groups will be as follows: All patients in group 1 will undergo discontinuation of MPA and will receive Zortress (everolimus) 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 continue with tacrolimus (target trough level of 6-10 ng/mL), prednisone, and undergo a 50% reduction of the MPA dose. At months 1, 2, and 3 post-randomization urine and plasma BKV levels will be re-checked. Renal allograft biopsies will be done for cause as clinically indicated. Tacrolimus trough levels are lower in the Zortress (everolimus) arm in order to minimize any potential nephrotoxicity with this drug combination as well as minimize the risk of over-immunosuppression.

In all patients, routine transplant monitoring labs will be performed monthly as part of standard of care including a measurement of BUN and Cr, CBC, tacrolimus trough levels, urine protein excretion and fasting lipids.

During the 3 month treatment period patients will be seen in clinic at baseline and months 1, 2, and 3 for follow-up. The assessment to address the primary objective will be performed at the end of the treatment period (Month 3). An interim analysis will be performed once 50% enrollment is reached.

In a sub-group of patients (30 patients total; 15 in group 1 and 15 in group 2) using our whole-blood assay measuring p70S6 kinase phosphorylation, the investigators will investigate the correlation between inhibition of p70S6 kinase phosphorylation with BKV replication. Finally, by measuring both p70S6 phosphorylation inhibition as well as expression of the NFAT-regulated genes IL-2, interferon gamma and GM-CSF, the investigators will correlate rejection episodes in patients maintained on lower immunosuppression alone versus those on a Zortress (everolimus) -based regimen. As patients are assigned to their intervention group based on the randomization scheme they will be offered enrollment in this sub-group analysis. All patients will be sequentially enrolled in the sub-group analysis until the 30 subject goal is reached with 15 subjects per group. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• BK Virus Infection
• Infection
• Virus Diseases

• NCT number: NCT01624948
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Completed
• Phase: Phase 4
• Start date: September 2012
• Completion date: November 2015