Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients (STeadfast)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04817774|
Recruitment Status : Recruiting
First Posted : March 26, 2021
Last Update Posted : June 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant Rejection End Stage Renal Disease||Biological: TX200-TR101||Phase 1 Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicentre Open-Label Single Ascending Dose Dose-Ranging Phase I/IIa Study to Evaluate Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor TRegulatory Cell Therapy in Living Donor Renal Transplant Recipients|
|Actual Study Start Date :||March 17, 2021|
|Estimated Primary Completion Date :||November 13, 2024|
|Estimated Study Completion Date :||March 4, 2026|
Experimental: Treatment group
Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation, up to 15 subjects.
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 approximately 12 weeks post- transplant. Three, single ascending dose cohorts of TX200-TR101 are planned and an additional expansion cohort.
Other Name: CAR-Tregs
No Intervention: Control group and Transplant donors
Control group: Subjects undergo kidney transplant as per planned standard of care with no study drug administered, up to 6 subjects.
Transplant donors: Transplant donors for each subject in the treatment and control groups, up to 21 subjects.
- Safety and Tolerability [ Time Frame: 28 days post infusion ]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.
- Acute graft related outcomes [ Time Frame: Day of infusion through to Week 84 ]Incidence of biopsy confirmed acute rejection according to the Banff classification criteria
- Long-term safety [ Time Frame: Day of infusion through to Week 84 ]Number of transplant recipient subjects with TEAEs, including SAEs, as assessed by CTCAE v5.0
- Immunosuppression [ Time Frame: Day of infusion through to Week 84 ]Ability to reduce immunosuppression as measured by the proportion of subjects receiving tacrolimus monotherapy at Week 84
- Graft localization [ Time Frame: Day of infusion through to Week 84 ]Graft localization of TX200-TR101 cells as measured by the presence of CD4+ CAR+ cells in the renal transplant biopsy
- Chronic graft related outcomes [ Time Frame: Day of infusion through to Week 84 ]Chronic graft dysfunction as measured by estimated glomerular filtration rate
- Chronic graft related outcomes [ Time Frame: Day of infusion through to Week 84 ]Incidence of chronic graft rejection according to the Banff criteria for chronic rejection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04817774
|Contact: Sangamo Patient Advocacyemail@example.com|
|University Hospitals Leuven||Recruiting|
|Contact: Dirk Kuypers, Dr. +32 16 344586 firstname.lastname@example.org|
|University Medical Center Groningen||Recruiting|
|Contact: J.S.F Sanders, Dr. 050-3612955 email@example.com|
|Oxford University Hospitals NHS Foundation Trust,||Recruiting|
|Oxford, United Kingdom|
|Contact: Paul Harden, Dr. +44 (0) 1865228659 Paul.firstname.lastname@example.org|