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

Primary Purpose

Kidney Transplant Rejection, End Stage Renal Disease

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

TX200-TR101

About this trial

This is an interventional prevention trial for Kidney Transplant Rejection focused on measuring Regulatory T cells, Genetically modified cells, Chimeric Antigen Receptor, Living donor, Autologous

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospitals LeuvenRecruiting
Charité UniversitätsmedizinRecruiting
University Medical Center GroningenRecruiting
Leiden University Medical CentreRecruiting
Erasmus MC, University Medical CenterRecruiting
Oxford University Hospitals NHS Foundation Trust,Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment group

Control group and Transplant donors

Arm Description

Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation, up to 15 subjects.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Acute graft related outcomes

Incidence of biopsy confirmed acute rejection according to the Banff classification criteria

Long-term safety

Number of transplant recipient subjects with TEAEs, including SAEs, as assessed by CTCAE v5.0

Immunosuppression

Ability to reduce immunosuppression as measured by the proportion of subjects receiving tacrolimus monotherapy at Week 84

Graft localization

Graft localization of TX200-TR101 cells as measured by the presence of CD4+ CAR+ cells in the renal transplant biopsy

Chronic graft related outcomes

Chronic graft dysfunction as measured by estimated glomerular filtration rate

Chronic graft related outcomes

Incidence of chronic graft rejection according to the Banff criteria for chronic rejection

Full Information

NCT ID

NCT04817774

First Posted

March 9, 2021

Last Updated

March 31, 2023

Sponsor

Sangamo Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04817774

Brief Title

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

Acronym

STeadfast

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 17, 2021 (Actual)

Primary Completion Date

November 13, 2024 (Anticipated)

Study Completion Date

March 4, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sangamo Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney Transplant Rejection, End Stage Renal Disease

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Arm Description

Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation, up to 15 subjects.

Arm Title

Control group and Transplant donors

Arm Type

No Intervention

Arm Description

Intervention Type

Biological

Intervention Name(s)

TX200-TR101

Other Intervention Name(s)

CAR-Tregs

Intervention Description

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. Three, single ascending dose cohorts of TX200-TR101 are planned and an additional expansion cohort.

Primary Outcome Measure Information:

Title

Safety and Tolerability

Description

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

Secondary Outcome Measure Information:

Title

Acute graft related outcomes

Description

Incidence of biopsy confirmed acute rejection according to the Banff classification criteria

Time Frame