The purpose of this study is to evaluate the safety and tolerability of TX200-TR101 and its effects on the donated kidney in living donor kidney transplant recipients. TX200-TR101 is a product made from a kidney transplant recipient's own immune cells, which are genetically modified and designed to help the transplant recipient's body accept their donated kidney and prevent their immune system from rejecting it.
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 three different types of participants - transplant recipients who will receive the study treatment TX200-TR101; control participants, who are transplant recipients who will not receive the study treatment; and transplant donors, who will donate their kidney to the transplant recipients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
26
TX200-TR101 is an autologous gene therapy medicinal product composed of Treg cells (CD4+/CD45RA+/CD25+/CD127low/neg) that have been ex vivo expanded and transduced with a lentiviral vector encoding for a CAR to recognize HLA-A\*02. Treatment will be given via an IV infusion at a pre-defined timepoint several weeks after transplant. Four, single ascending dose cohorts of TX200-TR101 are planned and an additional expansion cohort.
University Hospitals Leuven
Leuven, Belgium
University Medical Center Groningen
Groningen, Netherlands
Leiden University Medical Centre
Leiden, Netherlands
Erasmus MC, University Medical Center
Rotterdam, Netherlands
Safety and Tolerability
Safety and tolerability of TX200-TR101 infusion evaluated by incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.
Time frame: 28 days post infusion
Acute graft related outcomes
Incidence of biopsy confirmed acute rejection according to the Banff classification criteria
Time frame: Day of infusion through to Week 84
Long-term safety
Number of transplant recipient subjects with TEAEs, including SAEs, as assessed by CTCAE v5.0
Time frame: Day of infusion through to Week 84
Immunosuppression
Ability to reduce immunosuppression as measured by the proportion of subjects receiving tacrolimus monotherapy at Week 84
Time frame: Day of infusion through to Week 84
Graft localization
Graft localization of TX200-TR101 cells as measured by the presence of CD4+ CAR+ cells in the renal transplant biopsy
Time frame: Day of infusion through to Week 84
Chronic graft related outcomes
Chronic graft dysfunction as measured by estimated glomerular filtration rate
Time frame: Day of infusion through to Week 84
Chronic graft related outcomes
Incidence of chronic graft rejection according to the Banff criteria for chronic rejection
Time frame: Day of infusion through to Week 84
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Oxford University Hospitals NHS Foundation Trust,
Oxford, United Kingdom