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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: End Stage Renal Disease; Kidney Transplant Rejection
• Intervention / Treatment: Biological: TX200-TR101

Detailed Description

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
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • University Hospitals Leuven
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Centre
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus MC, University Medical Center
• United Kingdom
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Foundation Trust,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation.	Biological: TX200-TR101; 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.; Other Names: 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. Transplant donors: Transplant donors for each subject in the treatment and control groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	28 days post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute graft related outcomes	Incidence of biopsy confirmed acute rejection according to the Banff classification criteria	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	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	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	Day of infusion through to Week 84
Chronic graft related outcomes	Chronic graft dysfunction as measured by estimated glomerular filtration rate	Day of infusion through to Week 84
Chronic graft related outcomes	Incidence of chronic graft rejection according to the Banff criteria for chronic rejection	Day of infusion through to Week 84

Collaborators and Investigators

• Sponsor: Sangamo Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): July 11, 2024
• Study Completion (Estimated): October 29, 2025

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Autologous; Chimeric Antigen Receptor; Regulatory T cells; Genetically modified cells; Living donor
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: TX200 KT02; 2019-001730-34 (EudraCT Number); 2024-512579-11-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No