Long-Term Follow-Up of TX200-TR101 (STEADFAST Long Term)

Study Overview
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Brief Summary
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This long-term follow-up study is being conducted to collect long-term (up to 15 years post-infusion) safety and tolerability data from subjects enrolled in studies evaluating TX200-TR101.

Detailed Description
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This is long- term follow up observational trial for patients who participated previously to 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 this observational long-term follow up study (TX200-KT03) is to collect long-term (up to 15 years post-infusion) safety and tolerability data from subjects enrolled in studies evaluating TX200-TR101. In addition, the long-term effects and durability of the clinical effect of TX200-TR101 in subjects who received TX200-TR101 will be assessed and compared with control participants in the interventional Study (TX200- KT02).

Official Title
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Long-Term Follow-Up of Patients Who Have Received an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (CAR- Treg Therapy, TX200-TR101) in a Prior Clinical Study

Conditions
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Kidney Transplant Rejection, End Stage Renal Disease

Intervention / Treatment
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* Diagnostic Test: Urine sample
* Diagnostic Test: Blood sample
* Other: Lifestyle questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who enrolled in the Phase I/IIa study TX200-KT02, received a transplanted kidney and have either completed or withdrawn from that study. Willing and able to provide written informed consent (IC) in accordance with local regulations and governing Independent Ethics Committee (IEC)/Institutional Review Board (IRB) requirements prior to any procedure or evaluation performed specifically for the sole purpose of the study. Exclusion Criteria: N/A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment group<br>Subjects underwent a kidney transplant as per planned standard of care and were administered study drug TX200-TR101 in study TX200-KT02 post transplantation Assigned interventions - subjects who received TX200-TR101 in clinical study TX200-KT02 | Diagnostic Test: Urine sample<br>* Routine procedures<br>Diagnostic Test: Blood sample<br>* Routine procedures<br>Other: Lifestyle questionnaire<br>* Lifestyle questionnaire<br>|
| Control group<br>Subjects underwent a kidney transplant as per planned standard of care in study TX200-KT02 with no study drug administered, up to 6 subjects | Diagnostic Test: Urine sample<br>* Routine procedures<br>Diagnostic Test: Blood sample<br>* Routine procedures<br>Other: Lifestyle questionnaire<br>* Lifestyle questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of TX200-TR101 infusion evaluated by overall survival | Long term safety and tolerability of TX200-TR101 infusion evaluated by overall survival | Up to 15 years post infusion | 
| Safety and Tolerability TX200-TR101 infusion evaluated by and incidence of serious adverse events (SAEs) according to CTCAE V5.0. | Long term safety and tolerability of TX200-TR101 infusion evaluated by and incidence of serious adverse events (SAEs) according to CTCAE V5.0. | Up to 15 years post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term graft related outcomes | Incidence of graft rejection according to the Banff classification criteria | Up to 15 years post infusion | 
| Number of in-patient days in hospital to evaluate the effect of TX200-TR101 over a long term | Number of in-patient days in hospital | Up to 15 years post infusion | 
| Incidence of Adverse Events related to TX200-TR101 over a long term period | Incidence of Adverse Events related to TX200-TR101 | Up to 15 years post infusion | 
| Incidence of Adverse Events of special interest as defined in the protocol over long term | Incidence of Adverse Events of special interest as defined in the protocol | Up to 15 years post infusion | 
| Incidence of anti-drug antibodies against HLA A2 CAR Tregs to evaluate the effect of TX200-TR101 over a long term | Incidence of anti-drug antibodies against HLA A2 CAR Tregs | Up to 15 years post infusion | 
| Change in immunosuppression regime to evaluate long term safety of TX200-TR101 | Change in immunosuppression regime | Up to 15 years post infusion | 
| Incidence of graft loss due to rejection to evaluate the composite efficacy profile of TX200-TR101 | Incidence of graft loss due to rejection | Up to 15 years post infusion | 
| Incidents of deaths to evaluate composite efficacy profile of TX200-TR101 | Incidences of death of TX200-TR101 participants | Up to 15 years post infusion | 
| Incidence of chronic graft dysfunction measured by changes in estimated glomerular filtration rate to evaluate the composite efficacy profile of TX200-TR101 | Incidence of chronic graft dysfunction measured by changes in estimated glomerular filtration rate | Up to 15 years post infusion | 
| Impact on Quality of Life | SF-36 Questionnaire scaled with lower score meaning more disability scored ranging from 0-100 with 100 representing the highest health related quality of life | Up to 15 years post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Regulatory T-Cells, Genetically modified cells, Chimeric antigen receptor, Long term follow up, T-Regs, Cell Therapy