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

NCT01624948 | Completed Phase 4 Results

• 1 other identifier: CRAD001AUS184T
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

BK Virus Infection

Keywords

BK virus; Kidney Transplantation; Immunologic Monitoring

Outcome Measures

Primary Outcomes (1)

• Evidence of Reduction of BK Viruria and/or Clearance of BK Viremia

  composite outcome of a 50% or greater reduction in BKV urine levels and/or complete clearance of BKV viremia by 3 months after randomization

  3 months post-randomization

Secondary Outcomes (5)

• Evaluation for the Development of BK Virus Nephropathy or Doubling of BK Viremia Levels

  3 months post-randomization

• p70S6 Kinase Phosphorylation

  3 months post-randomization

• Cholesterol

  3 months post-randomization

• Proteinuria

  3 months post-randomization

• Median Between the Calculated Mean Residual Expression of NFAT-regulated Genes

  3 months post-randomization

Study Arms (2)

Everolimus+Tacrolimus/Prednisone

EXPERIMENTAL

This arm (group 1) will undergo mycophenolic acid (MPA) discontinuation with the addition of Zortress (everolimus) to their current regimen of tacrolimus and prednisone; All patients in group 1 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.

Drug: Everolimus

Standard of care: 50% reduction of MPA

ACTIVE COMPARATOR

This arm (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, which is the standard immunosuppression treatment for renal transplant recipients with evidence of BKV infection. 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.

Drug: Mycophenolic acid dose reduction

Interventions

Everolimus DRUG

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.

Also known as: Zortress

Everolimus+Tacrolimus/Prednisone

Mycophenolic acid dose reduction DRUG

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.

Also known as: CellCept, Myfortic

Standard of care: 50% reduction of MPA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.

  PMID: 39382091 DERIVED

MeSH Terms

Interventions

Everolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Allison Webber MD
• Organization: UCSF

allison.webber2@ucsf.edu

415 353 8382

Study Officials

• Allison Webber, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2012
• First Posted: June 21, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: November 1, 2015
• Last Updated: August 15, 2016
• Results First Posted: August 15, 2016

Record last verified: 2016-07

Locations

US (1)