Safety and Clinical Activity of QEL-001 in A2-mismatch Liver Transplant Patients

A Single-arm, Open-label, Multi-center, Phase I/II Study Evaluating the Safety and Clinical Activity of QEL-001, an Autologous CAR T Regulatory Cell Treatment Targeting HLA-A2, in HLA-A2/ A28neg Patients That Have Received an HLA-A2pos Liver Transplant.

The purpose of this study is to evaluate the safety and tolerability of QEL-001 in the prevention of liver transplant rejection following immunosuppression withdrawal. QEL-001 is a product made from a patients own cells, which are genetically modified and designed to help the transplant recipient's body accept their donated liver and prevent their immune system from rejecting it once immune suppression is withdrawn.

This study is a multicenter, first-in-human, open-label, single-arm study of an autologous CAR T regulatory (CAR-Treg) in HLA-A2 mismatched liver transplant recipients. The aim is for the CAR-Tregs to be activated on recognition of HLA-A2 antigens present on the donated liver and subsequently induce and maintain immunological tolerance to the organ.

Inclusion Criteria:

• Written informed consent.
• Subject who are HLA A2/A28 negative who have received HLA A2-mismatch liver transplant 12 months to 5 years prior to study entry.
• Able and willing to use contraception.
• Be on stable maintenance of immunosuppression for at least 12 weeks prior to study entry.

Exclusion Criteria:

• Severe cardiac, respiratory disease or any other major organ dysfunction.

• Subjects with prior non-liver solid organ or hematopoietic stem cell transplant.

• Known hypersensitivity to study medication ingredients, protocol defined immunosuppressive medications, or a significant allergic reaction to any drug.

• Positive serology for human immunodeficiency virus (HIV), active or latent tuberculosis (TB) or other clinically active local or systemic infection.

• Use of investigational agents within 3 months of screening.

• Subjects with history of autoimmune disease requiring use of immunosuppression or biologics within 24 months prior to study entry.

• Subject with history of malignancy in the past 5 years.

• Medical or social condition that is not compatible with adequate study follow-up and any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.

• Protocol defined laboratory value for the following parameters:

  • Alanine aminotransferase (ALT) and either alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT),
  • Kidney function e.g. eGFR,
  • White blood cells,
  • Hemoglobin,
  • Platelets.