Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients (STeadfast)
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|ClinicalTrials.gov Identifier: NCT04817774|
Recruitment Status : Recruiting
First Posted : March 26, 2021
Last Update Posted : April 3, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant Rejection End Stage Renal Disease||Biological: TX200-TR101||Phase 1 Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: Treatment group
Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation, up to 15 subjects.
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.
- 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.
- 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
- 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
- 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
- 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
- Chronic graft related outcomes [ Time Frame: Day of infusion through to Week 84 ]Chronic graft dysfunction as measured by estimated glomerular filtration rate
- 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
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.
|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|
- 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.
- 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:
- White blood cells
- Aspartate transaminase (AST) and or alanine transaminase (ALT)
- Total bilirubin
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
|Contact: Sangamo Patient Advocacyemail@example.com|
|University Hospitals Leuven||Recruiting|
|Contact: Dirk Kuypers, Dr. +32 16 344586 firstname.lastname@example.org|
|Berlin, Germany, 10117|
|Contact: Fabian Halleck +49 30 450 553 243 email@example.com|
|University Medical Center Groningen||Recruiting|
|Contact: J.S.F Sanders, Dr. 050-3612955 firstname.lastname@example.org|
|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 email@example.com|
|Oxford University Hospitals NHS Foundation Trust,||Recruiting|
|Oxford, United Kingdom|
|Contact: Paul Harden, Dr. +44 (0) 1865228659 Paul.firstname.lastname@example.org|
|Responsible Party:||Sangamo Therapeutics|
|Other Study ID Numbers:||
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|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Regulatory T cells
Genetically modified cells
Chimeric Antigen Receptor
Kidney Failure, Chronic
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases
Renal Insufficiency, Chronic