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

NCT04817774 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: TX200 KT022019-001730-342024-512579-11-00
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 5

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.

Conditions

Kidney Transplant Rejection; End Stage Renal Disease

Keywords

Regulatory T cells; Genetically modified cells; Chimeric Antigen Receptor; Living donor; Autologous

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Acute graft related outcomes

  Day of infusion through to Week 84

• Long-term safety

  Day of infusion through to Week 84

• Immunosuppression

  Day of infusion through to Week 84

• Graft localization

  Day of infusion through to Week 84

• Chronic graft related outcomes

  Day of infusion through to Week 84

Study Arms (2)

Treatment group

EXPERIMENTAL

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

Biological: TX200-TR101

Control group and Transplant donors

NO INTERVENTION

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.

Interventions

TX200-TR101 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.

Also known as: CAR-Tregs

Treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Women of childbearing potential: negative pregnancy test
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sangamo Therapeutics: lead

Study Sites (5)

University Hospitals Leuven

Leuven, Belgium

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Leiden University Medical Centre

Leiden, 2333 ZA, Netherlands

Location

Erasmus MC, University Medical Center

Rotterdam, 3015 CN, Netherlands

Location

Oxford University Hospitals NHS Foundation Trust,

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 26, 2021
• Study Start: March 17, 2021
• Primary Completion: July 11, 2024
• Study Completion: October 29, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); GB (1); NL (3)