BK Virus Nephropathy After Kidney TransplantationPhase 4BK EVERNCT03216967
Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia.
A Phase 4 study testing everolimus in people with BK Virus Nephropathy After Kidney Transplantation, run by University Hospital, Strasbourg, France at 15 sites in France.
Trial summary
BK virus nephropathy (BKVN), a consequence of the strong immunosuppressive therapy given after kidney transplantation, represents a growing problem in the kidney transplant (KT) setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- BK Virus Nephropathy After Kidney Transplantation
- What is being tested?
- everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 15 sitesFrance
- Study dates
- 15 Jan 2018to 1 Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients
- Kidney transplant recipients
- Patients treated by a calcineurin inhibitor and mycophenolic acid
- Viremia >= 2.8 log UI/ml
- Patients who have given written informed consent
- Negative pregnancy test (blood β-HCG dosage)
Who cannot join
- Known proved BKV nephropathy
- Hypersensitivity to everolimus, sirolimus or excipient
- Concomitant treatment by leflunomide, cidofovir, sirolimus, Millepertuis (Hypericum Perforatum)
- Pregnant or lactating women
- Women of child bearing potential unless they are using a birth control method
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
CHU - Hôpital Sud
Amiens, 80054
CHRU d'Angers
Angers, 49033
CHU - Hôpital de la Cavale Blanche
Bois-Guillaume, 76230
CHU - Hôpital de la Cavale Blanche
Brest, 29609
CHU Côte de Nacre
Caen, 14033
CHU Hôpital Gabriel Montpied
Clermont-Ferrand, 63000
CHU - Hôpital Dupuytren
Limoges, 87042
Hôpital Edouard Herriot
Lyon, 69003
AP-HP Hôpital Necker
Paris, 75743
AP-HP - Hôpital Georges Pompidou
Paris, 75908
CHU Poitiers - Hôpital Jean Bernard
Poitiers, 86021
CHU - Hôpital Maison Blanche
Reims, 51092
CHU Rennes - Hôpital Pontchaillou
Rennes, 35033
Les Hôpitaux Universitaires
Strasbourg, 67000
CHRU - Hôpital Bretonneau
Tours, 37044
About this study
Official title: Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia After Reduction of Immunosuppression Alone vs. Reduction of Immunosuppression and Replacement of Mycophenolate Mofetil by Everolimus
BK virus nephropathy (BKVN), a consequence of the strong immunosuppressive therapy given after kidney transplantation, represents a growing problem in the kidney transplant (KT) setting. In recent cohorts, BKVN concerns up to 10% of kidney transplant recipients and early signs of BK virus (BKV) infection as development of asymptomatic viruria and viremia are even much more frequent (40% and 20% of patients, respectively). In this context, finding strategies to prevent BKV infection or treat patients before the occurrence of BKV nephropathy is challenging. For several years, detection of BKV replication by real-time PCR in urine and/or blood of kidney transplant recipients at early stages of infection allowed adaptation of their therapy. As BKV reactivates essentially in patients with over-immunosuppression, the first step of the treatment is the reduction of immunosuppression. However, reducing immunosuppression (IS) can lead to acute rejection and allograft loss. Other treatments have been proposed (cidofovir, quinolones) but their toxicity profile or their lack of clinical efficacy are now demonstrated. Hence, an efficient and safe strategy against uncontrolled BKV replication is urgently needed. MTor-inhibitors are well known immunosuppressive drugs used in organ transplantation to prevent graft-rejection. They have furthermore anti-viral effects that can be beneficial for prevention of viral infections after transplantation. Recent evidence that inhibition of mTor pathway had an impact on BK infected cells provides additional insight into the observed benefits associated with these drugs. The aim of our study is to evaluate the effect of the mTor inhibitor everolimus on the prevention of severe BKV infection (BKV nephropathy or loss of the allograft) after kidney transplantation compared to the reduction of immunosuppression alone in kidney recipients with BK viremia.
- Being tested
- everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Patients with viremia above 2.8 log of copies/ml will be randomized (ratio 1:1) into either of 2 groups Group 1 : control group : immunosuppression lowering or Group 2 : experimental group : immunosuppression lowering and replacement of mycophenolate acid by everolimus Evolution of BKV viremia and allograft function will be assessed during 2 years after randomization
| Study group | Role | What they receive |
|---|---|---|
| IS lowering alone | Active comparator | 50% decrease of the dose of mycophenolic acid at M1 (target AUC 20 mg.h/L) Receives: Drug: everolimus |
| Everolimus + IS lowering | Experimental | Stop mycophenolate acid (Cellcept or myfortic) Introduction of everolimus : 2 x 0.75 mg/d per os in patiens treated by ciclosporine Receives: Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The main objective of our study is to evaluate the proportion of patients with BKV clearance 6 months after introduction of everolimus in kidney recipients who develop BKV viremia compared to patients managed with IS reduction alone
The primary end point is the proportion of patients with clearance of BK viremia assessed by blood PCR and functional graft 6 months after modification of immunosuppressive therapy
Measured: 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2017
- Study start15 Jan 2018
- Primary completion1 Aug 2024
- Study completion1 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BK Virus Nephropathy After Kidney TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03216967
- Sponsor's protocol ID
- 6646
- Acronym
- BK EVER
- Status last verified
- Sep 2025
- First submitted
- 4 Jul 2017
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Caillard S, Meyer N, Solis M, Bertrand D, Jaureguy M, Anglicheau D, Ecotiere L, Buchler M, Bouvier N, Schvartz B, Rerolle JP, Heng AE, Couzi L, Duveau A, Morelon E, LeMeur Y, Golbin L, Thervet E, Benotmane I, Fafi-Kremer S. Insights from the BKEVER Trial comparing everolimus versus mycophenolate mofetil for BK Polyomavirus infection in kidney transplant recipients. Kidney Int. 2025 Feb;107(2):338-347. doi: 10.1016/j.kint.2024.09.018. Epub 2024 Oct 28.
PubMed 39490986
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Randomized Two-arms Study Evaluating the BK Viral Clearance in Kidney Transplant Recipients With BK Viremia After Reduction of Immunosuppression Alone vs. Reduction of Immunosuppression and Replacement of Mycophenolate Mofetil by Everolimus
- ClinicalTrials.gov ID
- NCT03216967
- Acronym / sponsor ID
- BK EVER / 6646
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Aug 2024 (actual)
- First posted
- 13 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BK virus nephropathy (BKVN), a consequence of the strong immunosuppressive therapy given after kidney transplantation, represents a growing problem in the kidney transplant (KT) setting. In recent cohorts, BKVN concerns up to 10% of kidney transplant recipients and early signs of BK virus (BKV) infection as development of asymptomatic viruria and viremia are even much more frequent (40% and 20% of patients, respectively). In this context, finding strategies to prevent BKV infection or treat patients before the occurrence of BKV nephropathy is challenging. For several years, detection of BKV replication by real-time PCR in urine and/or blood of kidney transplant recipients at early stages of infection allowed adaptation of their therapy. As BKV reactivates essentially in patients with over-immunosuppression, the first step of the treatment is the reduction of immunosuppression. However, reducing immunosuppression (IS) can lead to acute rejection and allograft loss. Other treatments have been proposed (cidofovir, quinolones) but their toxicity profile or their lack of clinical efficacy are now demonstrated. Hence, an efficient and safe strategy against uncontrolled BKV replication is urgently needed. MTor-inhibitors are well known immunosuppressive drugs used in organ transplantation to prevent graft-rejection. They have furthermore anti-viral effects that can be beneficial for prevention of viral infections after transplantation. Recent evidence that inhibition of mTor pathway had an impact on BK infected cells provides additional insight into the observed benefits associated with these drugs. The aim of our study is to evaluate the effect of the mTor inhibitor everolimus on the prevention of severe BKV infection (BKV nephropathy or loss of the allograft) after kidney transplantation compared to the reduction of immunosuppression alone in kidney recipients with BK viremia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IS lowering alone | Active comparator | Drug: everolimus50% decrease of the dose of mycophenolic acid at M1 (target AUC 20 mg.h/L) |
| Everolimus + IS lowering | Experimental | Drug: everolimusStop mycophenolate acid (Cellcept or myfortic) Introduction of everolimus : 2 x 0.75 mg/d per os in patiens treated by ciclosporine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients
- Kidney transplant recipients
- Patients treated by a calcineurin inhibitor and mycophenolic acid
- Viremia >= 2.8 log UI/ml
- Patients who have given written informed consent
Key exclusion criteria (5 listed)
- Known proved BKV nephropathy
- Hypersensitivity to everolimus, sirolimus or excipient
- Concomitant treatment by leflunomide, cidofovir, sirolimus, Millepertuis (Hypericum Perforatum)
- Pregnant or lactating women
- Women of child bearing potential unless they are using a birth control method
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusPatients with viremia above 2.8 log of copies/ml will be randomized (ratio 1:1) into either of 2 groups Group 1 : control group : immunosuppression lowering or Group 2 : experimental group : immunosuppression lowering and replacement of mycophenolate acid by everolimus Evolution of BKV viremia and allograft function will be assessed during 2 years after randomization | Drug | Everolimus + IS lowering, IS lowering alone |
Primary outcome
The main objective of our study is to evaluate the proportion of patients with BKV clearance 6 months after introduction of everolimus in kidney recipients who develop BKV viremia compared to patients managed with IS reduction alone
Time frame: 6 months after randomization
The primary end point is the proportion of patients with clearance of BK viremia assessed by blood PCR and functional graft 6 months after modification of immunosuppressive therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Results publication: PubMed 39490986Caillard S, Meyer N, Solis M, Bertrand D, Jaureguy M, Anglicheau D, Ecotiere L, Buchler M, Bouvier N, Schvartz B, Rerolle JP, Heng AE, Couzi L, Duveau A, Morelon E, LeMeur Y, Golbin L, Thervet E, Benotmane I, Fafi-Kremer S. Insights from the BKEVER Trial comparing everolimus versus mycophenolate mofetil for BK Polyomavirus infection in kidney transplant recipients. Kidney Int. 2025 Feb;107(2):338-347. doi: 10.1016/j.kint.2024.09.018. Epub 2024 Oct 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing everolimus in people with BK Virus Nephropathy After Kidney Transplantation, run by University Hospital, Strasbourg, France at 15 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The main objective of our study is to evaluate the proportion of patients with BKV clearance 6 months after introduction of everolimus in kidney recipients who develop BKV viremia compared to patients managed with IS reduction alone (time frame: 6 months after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03216967, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.