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Kidney Transplant InfectionPhase 1NCT05042076

BK With VST for Kidney Transplant Patients

A Phase 1 study testing BK-specific T cells from Donor Lymphocytes in people with Kidney Transplant Infection and BK Virus Infection, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study measures the safety, feasibility, and efficacy of viral-specific T cells (VST) against BK Virus (BKV) in adult kidney transplant recipients. Participants are expected to be on study for 52 weeks. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
What is being tested?
BK-specific T cells from Donor Lymphocytes
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
16 Dec 2021to 14 May 2024
Phase
Phase 1
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 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age18 ≤ 75 years
  • Have BKV infection/viremia following kidney transplantation, where BKV viremia is defined as positive BKV qPCR (≥ 250 copies)
  • Have evidence of invasive BKV infection (BK Nephropathy)
  • Experience one of the following:
  • New, persistent and/or worsening BKV-related symptoms, signs and/or markers of end organ compromise despite being on lower immunosuppressive medication
  • Adverse effects of lower immunosuppressive medications (e.g., dnDSA, biopsy proven rejection)
  • Eligible Donor
  • Provide Written informed consent

Who cannot join

  • Non-kidney organ transplant recipient
  • Patient with acute rejection of the kidney allograft at time of T-cell transfer
  • Patient receiving steroids (>0.5 mg/kg body weight (BW) prednisone equivalent) at the time of T-cell transfer
  • Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive monoclonal antibodies within 28 days prior to T-cell transfer
  • Extra renal tissue invasive BK infection
  • Concomitant enrollment in another clinical trial interfering with endpoints of this study
Show all 22Show fewer
  • Any medical condition which could compromise participation in the study according to the investigator's assessment
  • Known HIV infection
  • Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control during study treatment Note: Women of childbearing potential must have a negative urine pregnancy test at study entry.
  • Patients unwilling or unable to comply with the protocol or unable to give informed consent
  • Donor Eligibility
  • ≥ 18 years old
  • Available and capable of undergoing a single standard 2 blood volume leukapheresis
  • HLA Compatible (see Donor selection priority below):
  • Original kidney transplant donor
  • Fully HLA matched family member (6/6 HLA match considering HLA-A, HLA-B and HLA-DRB1 genes)
  • Partially matched family member (≥ 2/6 HLA match, considering HLA-A, HLA-B and HLA-DRB1 genes)
  • BK IgG seropositive
  • Meets the criteria for donor eligibility defined in the UW Program for Advanced Cell Therapy Standard Operating Policies and Procedures for Donor Evaluation and Eligibility Determination for the Donation of Viral Specific T Cells, which is in compliance with FACT standards for Immune Effector Cells, and 21 CFR 1271, subpart C.
  • Provide written informed consent
  • Donor selection priority: The original kidney donor will be the first choice of donor peripheral mononuclear cells. If the original donor is not available or does not meet all donor eligibility criteria, alternative related donors will be selected, with preference for fully matched related donors (6/6 HLA match, considering HLA-A, -B, and -DRB1 genes) over related donors with partial HLA match (≥ 2/6 HLA match, considering HLA-A, -B, and -DRB1 genes).
  • Note that if the selected donor is related, but not a biological parent or child of the recipient (i.e., at least haploidentical), then high resolution testing of HLA-A and HLA-B will be performed on donor and recipient (if high resolution HLA genotyping not already available in the medical record). If the degree of matching at high resolution reveals a less favorable match than an alternative donor, then prioritization of the alternative donor will occur.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53705

Other trials in United States

About this study

Official title: A Phase I Study Evaluating Safety and Tolerability of Viral-Specific T (VST) Cells Against BK Virus (BKV) in Adult Kidney Transplant Recipients

This study measures the safety, feasibility, and efficacy of viral-specific T cells (VST) against BK Virus (BKV) in adult kidney transplant recipients. Participants are expected to be on study for 52 weeks.

Read the detailed description

Viral infections, or their reactivation in the immunocompromised host, remain serious complications that adversely affect outcomes of transplantation. These infections may be refractory to pharmacologic treatment and result in increased morbidity and mortality after transplantation. Furthermore, the available pharmacologic therapies can result in severe toxicities.

Once an infection occurs, adequate immune reconstitution is decisive for recovery from viral disease after kidney transplantation. The present trial will consist of the treatment of kidney transplant recipients diagnosed with severe BK infection as defined by a viral load ≥ 250 copies/mL and BKN, with virus-specific, antigen-selected T cells using the CliniMACS® Prodigy System. BK-specific T cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior studies on transfer of CMV-specific T cells have been shown to be safe and efficacious in the treatment of Cytomegalovirus (CMV) infections, so the same methods will be used to transfer BK-specific T cells.

The main trial objective is to evaluate the safety and feasibility of BK-specific T-cell transfer in adult patients suffering from BK infections following kidney transplantation. The incubation with viral antigens (MACS Good Manufacturing Practice (GMP) PepTivator) allows the enrichment of BK-specific CD4+ and CD8+ T cells. Increasing evidence of the safety and efficacy of CMV-specific T-cell is available. Furthermore, the safety and efficacy of the specific manufacturing approach using the fully automated protocol of the CliniMACS® Prodigy for the isolation of CMV-specific T cells against CMV has been described and has demonstrated that these cells retain their biological properties. Based on the CMV data, the investigators believe BK-specific T cells will follow the same pattern.

Study Overview

This phase I, open label, non-randomized, non-placebo controlled, single group assignment study will assess the safety and tolerability of transfer of BK-specific T cells isolated from a leukapheresis product. Secondary objectives will focus on the feasibility and efficacy of the BK-specific T-cell transfer. The Investigational Medicinal Product (IMP) will be generated automatically by the CliniMACS® Prodigy using the CliniMACS Cytokine Capture System (IFNγ) after incubation with MACS GMP PepTivator® BKV LT \& VP1 for enrichment of virus-specific T-cells in adult patients suffering from BK infections following kidney transplantation.

Safety and tolerability will be assessed by determining the incidence and severity of acute infusion-related toxicities, incidence and severity of acute rejection of the kidney allograft, occurrence and time to newly occurring acute GVHD grade ≥1 until Week 12 after T-cell transfer, and aggravation of pre-existing acute GVHD grade ≥1 until Week 12.

Feasibility of BK virus specific T-cells will be assessed by determining the successful production of BK-VST from donors on an intent-to-treat basis, measuring dropout rate and reasons for drop out as well as time from patient inclusion to administration of the IMP.

Efficacy will be assessed by determining the number of patients and time to reaching ≥1 log decrease in BK viral load, number of patients with BK clearance, time to BK clearance, and number of patients with resolution of clinical BK organ disease by Week 12. Number of BK reactivations following BK viral clearance and overall survival (OS) will be determined at Week 52.

Being tested
BK-specific T cells from Donor Lymphocytes
Keywords
virus specific T lymphocyte, VST

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BK-specific T cells from Donor LymphocytesDrug

    Naturally occurring, allogeneic donor lymphocytes derived from a leukapheresis, enriched for BK-specific CD4+ and CD8+ T cells

    Suspension of BK-specific T cells in approximately 7 mL (5-10 mL range for volume of IMP) of 0.9% NaCl with 2.5% HSA at a cell dose of: ≥ 300 and ≤ 5,000 BK virus-specific CD3+ T cells/kg body weight (BW).

    IV bolus injection; IV push of IMP over approximately 2-4 minutes, resulting in an infusion rate of approximately 3 mL/min.

Study groups in NCT05042076
Study groupRoleWhat they receive
BK with VSTExperimentalAdult patients with BKV infection and nephropathy (BKN) following kidney transplantation.
Receives: Drug: BK-specific T cells from Donor Lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events up to 4 hours post Cell Infusion

    Safety of the intervention against BKV (BKV-VST) in adult kidney transplant recipients is in part measured by incidence of acute infusion-related toxicity on the day of T-cell transfer evaluated by measuring vital signs prior to and at different time points after the T-cell transfer and monitoring of specific adverse events (chills, nausea, vomiting, diarrhea, abdominal pain, allergic reactions, respiratory dysfunction or headache from T-cell transfer to 4 hours post injection).

    Measured: cell infusion is on study day 0, safety data collected up to 4 hours post injection

  2. Incidence of Adverse Events up to 4 weeks of T-cell Transfer

    Safety of the intervention against BKV (BKV-VST) in adult kidney transplant recipients is in part measured by incidence of grade 3-5 infusion-related adverse events, grades 4-5 non-hematological adverse events within 4 weeks of T-cell transfer that are not due to the pre-existing infection or original malignancy or pre-existing co-morbidities.

    Measured: up to 4 weeks

  3. Incidence of newly occurring acute rejection of kidney allograft until Week 12 after T-cell transfer

    Incidence and severity of acute rejection of the kidney allograft is in part measured by incidence of newly occurring acute rejection of kidney allograft until Week 12 after T-cell transfer.

    Measured: up to 12 weeks

  4. Incidence of de novo antibodies against kidney allograft donor (dnDSA) until Week 52 after T-cell transfer

    Incidence and severity of acute rejection of the kidney allograft is in part measured by incidence of de novo antibodies against kidney allograft donor (dnDSA) until Week 52 after T-cell transfer.

    Measured: up to 52 weeks

  5. Incidence of newly occurring acute GVHD grade ≥1 or aggravation of pre-existing acute GVHD until Week 12 after T-cell transfer

    Incidence and severity of Graft-versus-host disease (GVHD) is in part measured by the incidence of newly occurring acute GVHD grade ≥1 or aggravation of pre-existing acute GVHD until Week 12 after T-cell transfer.

    Measured: up to 12 weeks

  6. Incidence of newly occurring acute GVHD grade ≥1 from Day 0 to Week 12

    Incidence and severity of GVHD is in part measured by the incidence of newly occurring acute GVHD grade ≥1 from Day 0 to Week 12.

    Measured: up to 12 weeks

Secondary outcomes (11)

  1. Incidence of successful production of BK Virus specific T lymphocyte (VST) from donors on intent-to-treat basis

    Evaluation of feasibility of BK specific T cell transfer in adult participants suffering from severe BKV infection following kidney transplantation is in part measured by the successful production of BK Virus specific T lymphocyte (VST) from donors on intent-to-treat basis

    Measured: up to 1 week

  2. Number of Participants who Drop-out of the Study

    Evaluation of feasibility of BK specific T cell transfer in adult participants suffering from severe BKV infection following kidney transplantation is in part measured by the participant drop out rate.

    Measured: up to 52 weeks

  3. Summary of Reasons why Participants Drop-out of the Study

    Evaluation of feasibility of BK specific T cell transfer in adult participants suffering from severe BKV infection following kidney transplantation is in part evaluated by the reasons that participants drop out of the study.

    Measured: up to 52 weeks

  4. Time from Participant inclusion to administration of BK-VST

    Evaluation of feasibility of BK specific T cell transfer in adult participants suffering from severe BKV infection following kidney transplantation is in part measured by the amount of time from participant inclusion to administration of BK-VST.

    Measured: up to 1 week

  5. Percentage of Participants with ≥1 log decrease in BK viral load at Week 12

    Evaluation of efficacy of BK-specific T-cell transfer in adult participants suffering from severe BK infection following kidney transplantation is in part measured by the percentage of participants with ≥1 log decrease in BK viral load at Week 12.

    Measured: up to week 12

  6. Amount of Time to 1 log change in BK viral load

    Evaluation of efficacy of BK-specific T-cell transfer in adult participants suffering from severe BK infection following kidney transplantation is in part measured by the amount of time to 1 log change in BK viral load.

    Measured: up to week 12

  7. Number of Participants with BKV clearance from Day 7 to Week 12 after T-cell transfer

    Evaluation of efficacy of BK-specific T-cell transfer in adult participants suffering from severe BK infection following kidney transplantation is in part measured by the number of participants with BKV clearance (defined as 2 consecutive test results occurring at least 2 weeks apart with results that are either negative polymerase chain reaction (PCR) or <250 copies/mL) from Day 7 to Week 12 after T-cell transfer.

    Measured: up to week 12

  8. Amount of Time to BKV clearance from Day 0 of T-cell transfer to first day of 2 subsequent negative BKV PCR studies

    Evaluation of efficacy of BK-specific T-cell transfer in adult participants suffering from severe BK infection following kidney transplantation is in part measured by the amount of time to BKV clearance (defined as either negative PCR or <250 copies/mL) from Day 0 of T-cell transfer to first day of 2 consequent negative BKV PCR studies at least 2 weeks apart.

    Measured: up to week 12

  9. Number of Participants with resolution of underlying BKV infection from Day 7 (Week 1) to Week 12 after T-cell transfer as compared to Day 0

    Clinical response/resolution of underlying viral infection is measured by the number of participants with resolution of underlying BKV infection from Day 7 (Week 1) to Week 12 after T-cell transfer as compared to Day 0.

    Measured: up to 12 weeks

  10. Number of BKV reactivations following initial viral clearance until Week 52

    Effect on BKV reactivation is measured by the number of BKV reactivations following initial viral clearance until Week 52 .

    Measured: up to week 52

  11. Overall Survival (OS) Rate

    OS rate: time from T-cell transfer (Day 0) to death, graft loss, or last follow-up throughout the study from Day 1 to Week 52.

    Measured: up to week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2021
  2. Study start16 Dec 2021
  3. Primary completion14 May 2024
  4. Study completion14 May 2024

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single-center, Phase I, open label, non-randomized, non-placebo controlled
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05042076
Sponsor's protocol ID
2021-1058
Other IDs
A534280, Protocol Version 6/8/2022, Galipeau SMPH-PACT Support
Status last verified
Dec 2024
First submitted
3 Sep 2021
Last updated
10 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ptak L, Meyers RO, Radko-Ganz O, McDowell KA, Jorgenson M, Chilsen M, Mandelbrot D, Galipeau J, Parajuli S. A Phase I Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against BK-Virus in Adult Kidney Transplant Recipients. J Med Virol. 2025 Apr;97(4):e70357. doi: 10.1002/jmv.70357.

    PubMed 40249038

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BK-specific T cells from Donor Lymphocytes in people with Kidney Transplant Infection and BK Virus Infection, run by University of Wisconsin, Madison at 1 site in United States.

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 8 inclusion and 22 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 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Incidence of Adverse Events up to 4 hours post Cell Infusion (time frame: cell infusion is on study day 0, safety data collected up to 4 hours post injection). The study lists 6 primary outcomes in all. 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 NCT05042076, 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 10 Dec 2024.

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