BK With VST for Kidney Transplant Patients

NCT05042076 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: 2021-1058A534280Protocol Version 6/8/2022Galipeau SMPH-PACT Support
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Transplant Infection; BK Virus Infection

Keywords

virus specific T lymphocyte; VST

Outcome Measures

Primary Outcomes (6)

• 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).

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

• 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.

  up to 4 weeks

• 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.

  up to 12 weeks

• 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.

  up to 52 weeks

• 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.

  up to 12 weeks

• 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.

  up to 12 weeks

Secondary Outcomes (11)

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

  up to 1 week

• Number of Participants who Drop-out of the Study

  up to 52 weeks

• Summary of Reasons why Participants Drop-out of the Study

  up to 52 weeks

• Time from Participant inclusion to administration of BK-VST

  up to 1 week

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

  up to week 12

Study Arms (1)

BK with VST

EXPERIMENTAL

Adult patients with BKV infection and nephropathy (BKN) following kidney transplantation.

Drug: BK-specific T cells from Donor Lymphocytes

Interventions

BK-specific T cells from Donor Lymphocytes DRUG

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.

BK with VST

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53705, United States

Location

Study Officials

• Sandesh Parajuli, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Jacques Galipeau, MD

  University of Wisconsin, Madison

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, Phase I, open label, non-randomized, non-placebo controlled

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 13, 2021
• Study Start: December 16, 2021
• Primary Completion: May 14, 2024
• Study Completion: May 14, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)