Safety and efficacy of steering of immunosuppression based on BKPyV-specific T cells in case of BK Polyomavirus (BKPyV) DNAemia after kidney transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Paediatrisches Forschungsnetzwerk gGmbH, PROFIL Institut fuer Stoffwechselforschung GmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Phenomena and Processes [G] - Immune system processes [G12]

Decision date (initial)

2025-04-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BMBF, Förderkennzeichen 01KG2407

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate that not reducing immunosuppressive therapy (experimental group) is non-inferior to reducing immunosuppressive therapy according to standard of care guidelines (control group) with regard to the time to end of BKPyV-DNAemia for kidney transplanted patients diagnosed with BKPyV-DNAemia (≥ 10,000 IU/ml) and BKPyV-specific CD4 T cells ≥0.5 cells/µl.

Secondary objectives 3

1. To demonstrate that not reducing immunosuppressive therapy (experimental group) is superior to reducing immunosuppressive therapy (control group) with regard to renal function. enal function.
2. To evaluate the correlation between BKPyV-specific CD4 T cells, doses and trough levels of immunosuppressants.
3. To show that treatment decision based on BKPyV-specific CD4 T cells is feasible.

Conditions and MedDRA coding

BK Polyomavirus DNAemia after kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Kidney transplantation (also as part of multi-organ transplantations)
2. BKPyV-DNAemia (≥ 10,000 IU/ml) and BKPyV-specific CD4 T cells ≥0.5 cells/µl.
3. For women of childbearing potential (WCBP) (A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).): a negative serum pregnancy test with a sensitivity equal to at least 50 mIU/ml before study start and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive method with a failure rate of <1% per year during the treatment period.
4. For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
5. Signed Informed Consent: Patients’ guardians or adult patients who are capable of understanding the purpose and risks of the study must be willing to give written informed consent and willing to participate in and comply with the study protocol. Patients between 7 and 18 years have to agree with the study in addition to the informed consent of the legally authorized representative.
6. Patients´ guardians or adult patients consent that in case of randomization to experimental arm change of IMP during study participation is not allowed.
7. Current immunosuppression regime with at least one or a combination of defined IMP within this protocol.
8. No change in immunosuppression regime within 4 weeks prior trial entry

Exclusion criteria 9

1. Pregnant or lactating women or intention of becoming pregnant during study treatment
2. Criteria which in the opinion of the investigator preclude for reasons of compliance, or for reasons of the patient’s safety
3. Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
4. Known hypersensitivity to any of IMP components which would interfere with IMP treatment
5. The use of fluoroquinolones or statins to prevent or treat
6. The use of cidofovir or leflunomide to treat BKPvV-DNAemia/-nephropathy
7. Patients receiving belatacept who are seronegative for the Epstein-Barr virus (EBV) or whose serostatus is unknown
8. Patients receiving azathioprine who meet any of the following conditions: o Suffering from a severe infection o Having significantly impaired liver or bone marrow function o Ongoing pancreatitis o Necessity to administer any live vaccine, particularly BCG, smallpox, or yellow fever
9. Participation in another interventional trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time from randomization to end of BKPyV-DNAemia, where end of BKPyV-DNAemia is defined as the first time point after randomization with BKPyV DNA <1,000 IU/ml or a decline in BKPyV DNA of >1 log10 IU/ml (>90% curtailing) as the best-established surrogate marker in the literature for clearance of BKPyV infection.

Secondary endpoints 9

1. Change from baseline to month 9 in estimated glomerular filtration rate (eGFR)
2. Occurrence of acute rejection episodes
3. Occurrence of donor-specific antibodies
4. Occurrence of graft loss
5. Number and dose of immunosuppressants
6. Trough levels of immunosuppressants
7. Overall and CNI immunosuppressive scale (IS) units
8. Level of BKPyV-specific CD4 T cells
9. Occurrence of BKPyV re-infections

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Paediatrisches Forschungsnetzwerk gGmbH

Sponsor organisation

Paediatrisches Forschungsnetzwerk gGmbH

Address

Freiheit 1, Suedviertel Suedviertel

City

Essen

Postcode

45128

Country

Germany

Scientific contact point

Organisation

Paediatrisches Forschungsnetzwerk gGmbH

Contact name

Prof. Dr. Thurid Ahlenstiel-Grunow

Public contact point

Organisation

Paediatrisches Forschungsnetzwerk gGmbH

Contact name

Katharina Waack-Buchholz

Third parties 2

PROFIL Institut fuer Stoffwechselforschung GmbH

Sponsor organisation

PROFIL Institut fuer Stoffwechselforschung GmbH

Address

Hellersbergstrasse 9, Hammfeld Hammfeld

City

Neuss

Postcode

41460

Country

Germany

Public contact point

Organisation

PROFIL Institut fuer Stoffwechselforschung GmbH

Contact name

Dr. Tim Heise

Sponsor responsibilities

Article 77 compliance

Paediatrisches Forschungsnetzwerk gGmbH

Contact point sponsor

Paediatrisches Forschungsnetzwerk gGmbH

Article 77 implementation

Paediatrisches Forschungsnetzwerk gGmbH

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications