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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 : April 3, 2023
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

Study Description
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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.

Condition or disease Intervention/treatment Phase
Kidney Transplant Rejection End Stage Renal Disease Biological: TX200-TR101 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment group
Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation, up to 15 subjects.
 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. 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Chronic graft related outcomes [ Time Frame: Day of infusion through to Week 84 ]
    Chronic graft dysfunction as measured by estimated glomerular filtration rate

  6. 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


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women of childbearing potential: negative pregnancy test
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Sangamo Patient Advocacy +1-510-307-7266 clinicaltrials@sangamo.com

Locations
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Belgium
University Hospitals Leuven Recruiting
Leuven, Belgium
Contact: Dirk Kuypers, Dr.    +32 16 344586    dirk.kuypers@uzleuven.be   
Germany
Charité Universitätsmedizin Recruiting
Berlin, Germany, 10117
Contact: Fabian Halleck    +49 30 450 553 243    fabian.halleck@charite.de   
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: J.S.F Sanders, Dr.    050-3612955    j.sanders@umcg.nl   
Contact    050-3616161      
Leiden University Medical Centre Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Aiko P J de Vries, MD    +31 71 5298 114    A.P.J.de_Vries@lumc.nl   
Erasmus MC, University Medical Center Recruiting
Rotterdam, Netherlands, 3015 CN
Contact: Dennis Hesselink, M.D Ph.D    0614889537    d.a.hesselink@erasmusmc.nl   
United Kingdom
Oxford University Hospitals NHS Foundation Trust, Recruiting
Oxford, United Kingdom
Contact: Paul Harden, Dr.    +44 (0) 1865228659    Paul.harden@ouh.nhs.uk   
Sponsors and Collaborators
Sangamo Therapeutics
More Information
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Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT04817774    
Other Study ID Numbers: TX200 KT02
2019-001730-34 ( EudraCT Number )
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: April 3, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sangamo Therapeutics:
Regulatory T cells
Genetically modified cells
Chimeric Antigen Receptor
Living donor
Autologous
Additional relevant MeSH terms:
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Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
 Male Urogenital Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Chronic Disease
Disease Attributes
Pathologic Processes