A Study to Evaluate Posoleucel ALVR105 to Treat Kidney Transplant Recipients with BK Viremia

Overview

About this study

The purpose of this study of posoleucel ALVR105 is to assess the safety and tolerability of posoleucel ALVR105 in kidney transplant recipients. The key secondary objective is to test the hypothesis that the administration of posoleucel ALVR105 to kidney transplant recipients with BK viremia will demonstrate superiority in suppressing BK viral load compared with placebo.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Patients must be ≥18 years of age at the time of signing the informed consent.
  • Patients who had a kidney transplant performed ≥ 28 days prior to enrollment.
  • BKV, based on the following criteria (both must be met):
    • Any positive whole blood or plasma BK viral load at a local laboratory obtained ≤ 90 days before the start of screening;
    • Confirmation of BK viremia of 350 copies/mL – 10,000,000 copies/mL as determined by the central laboratory at screening.
  • At least 1 identified, suitably matched PSL cell line for infusion is available.
  • Male and/or female.
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male patients:
    • Male patients are eligible to participate if they agree to the following during the study treatment period and for at least 90 days after the last dose of study treatment;
    • Refrain from donating sperm; PLUS, either:
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR
    • Must agree to use contraception /barrier as detailed below:
    • Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant;
  • Female patients:
    • A female patient is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
    • She is a woman of non-childbearing potential (WONCBP); OR
    • She is a WOCBP and using an acceptable contraceptive method during the study treatment period and for at least 90 days after the last dose of study treatment. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study treatment;
    • A WOCBP must have a negative highly sensitive serum pregnancy test within 21 days before the first dose of study treatment.
  • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Exclusion Criteria:

  • Undergone allogeneic hematopoietic cell transplantation.
  • Evidence or history of GVHD or CRS.
  • Uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, fungemia, dissemination, and/or organ-specific infection not well controlled by present therapies).
  • Uncontrolled or progressive viral infections (ie, evidence of viremia, dissemination, and/or organ-specific infection not well controlled by present therapies) not targeted by PSL.
  • Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
  • Known or presumed pneumonia.
  • Hemodynamic or respiratory instability defined as either of the following:
    • Requirement for continuous infusions of inotropes or vasopressors for blood pressure support;
    • Requirement for endotracheal intubation or mechanical ventilation.
  • Evidence of any medical condition that in the opinion of the Investigator might interfere with the patient’s ability to participate in the trial.
  • Ongoing therapy with high-dose systemic corticosteroids (i.e, prednisone dose > 0.5 mg/kg/day or equivalent).
  • Patients who received, or are planned to receive, abatacept or belatacept, within 3 months of screening, or who received equine anti-thymocyte globulin ([ATG] Atgam®) or rabbit ATG (Thymoglobulin ®) in doses of > 4.5 mg/kg or alemtuzumab (Campath-1H) or other immunosuppressive T cell-targeted monoclonal antibodies < 28 days prior to randomization.
  • Receipt of other investigational antiviral treatments (e.g., anti-BK monoclonal antibodies) within 28 days or 5 half-lives (whichever is longer) prior to randomization.
  • Liver dysfunction, defined as liver transaminases (i.e., aspartate aminotransferase or alanine aminotransferase) >5 times the upper limit of normal (ULN) or direct bilirubin >2 times the ULN reference per local laboratory.
  • Renal dysfunction, defined as estimated glomerular filtration rate (eGFR) (estimated by Modified Dose in Renal Disease [MDRD] formula) < 20 mL/min/1.73 m^2.
  • Pregnant or nursing or planning to become pregnant.
  • ABO incompatible or complement-dependent lymphocytotoxic crossmatch positive transplant (isolated positive B cell crossmatches are not an exclusion criterion).
  • Weight < 40 kg.
  • History of hypersensitivity to an y of the components of the Investigational Product.

Eligibility last updated 12/9/21. Questions regarding updates should be directed to the study team contact.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Girish Mour, M.B.B.S., M.D.

Contact us for the latest status

Contact information:

Clinical Studies Unit

(904) 953-2255

More information

Publications

  • Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections. Read More on PubMed
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CLS-20529867

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