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

NCT ID: NCT04817774

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-17
• Study Completion Date: 2025-10-29

Brief Summary

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.

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.

Conditions

Kidney Transplant Rejection; End Stage Renal Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment group

Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation.

Group Type: EXPERIMENTAL

TX200-TR101

Intervention Type: BIOLOGICAL

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

CAR-Tregs

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangamo Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospitals Leuven

Leuven, , Belgium

University Medical Center Groningen

Groningen, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Erasmus MC, University Medical Center

Rotterdam, , Netherlands

Oxford University Hospitals NHS Foundation Trust,

Oxford, , United Kingdom

Countries

Belgium; Netherlands; United Kingdom

Other Identifiers

2019-001730-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-512579-11-00

Identifier Type: CTIS

Identifier Source: secondary_id

TX200 KT02

Identifier Type: -

Identifier Source: org_study_id