Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients

This is a multicentre, first-in-human, open-label, single ascending dose, dose-ranging study of autologous, chimeric antigen receptor T regulatory cells (CAR-Treg) in HLA-A2 mismatched living donor kidney transplant recipients, with a control cohort of mismatched kidney transplant recipients of similar immunological risk.The aim is for the CAR-Tregs to recognise the HLA-A2 molecule present on the donated kidney and subsequently induce and maintain immunological tolerance to the organ.

The study requires two arms - transplant recipients who will receive the study treatment TX200-TR101and control participants, who are transplant recipients who will not receive the study treatment.

Inclusion criteria

• Written informed consent.
• Male or female aged 18 - 70 years.
• Diagnosis of End Stage Renal Disease and waiting for a new kidney from an identified live donor.
• Subjects who will be single organ recipients (kidney).
• Able and willing to use contraception.

Exclusion criteria

• HLA identical to the donor.
• Subjects with prior organ 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) or syphilis, active or occult hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or other clinically active local or systemic infection.
• Subjects who are Epstein-Barr Virus (EBV) seronegative.
• Positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
• Subjects with panel-reactive antibody (PRA) >20% within 6 months prior to enrolment.
• Subjects with current or recent donor-specific antibodies.
• Use of any experimental medicinal product within 3 months.
• Current use of systemic immunosuppressive agents
• Significant unstable or poorly controlled acute or chronic diseases (except ESRD), limited life expectancy, clinically relevant central nervous system pathology, history of drug/alcohol abuse or psychiatric disorder or other condition that is not compatible with adequate study follow-up, history of malignancy in the past 5 years 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.
• Subjects with abnormal laboratory values in the following parameters:
• Haemoglobin
• Platelets
• White blood cells
• Aspartate transaminase (AST) and or alanine transaminase (ALT)
• Total bilirubin