Long-Term Follow-Up Study of TX200-TR101 in Patients with Kidney Transplant Rejection

The primary objective of this study is to evaluate the **safety** and **tolerability** of the TX200-TR101 infusion in patients who have previously received this therapy. This will be assessed by monitoring the incidence of serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The clinical relevance of this objective lies in ensuring that the autologous antigen-specific chimeric antigen receptor T regulatory cell therapy (CAR-Treg therapy) is safe for long-term use in patients who have undergone kidney transplant and are at risk of transplant rejection.

The secondary objective focuses on assessing long-term graft-related outcomes. This is crucial for understanding the sustained efficacy and potential benefits of the TX200-TR101 therapy in maintaining graft function and preventing rejection over an extended period.

The clinical trial involves a total of **10 participants** who are being evaluated for **Kidney Transplant Rejection**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating adult participants. The trial population was selected from individuals who had previously enrolled in the Phase I/IIa study TX200-KT02, received a transplanted kidney, and have either completed or withdrawn from that study. Participants are required to provide written informed consent in accordance with local regulations and governing Independent Ethics Committee/Institutional Review Board requirements. The study includes a vulnerable population, which necessitates careful ethical considerations. No specific lifestyle considerations such as diet or physical activity are mentioned in the available data.

The clinical trial is designed to evaluate the **safety** and **tolerability** of the investigational product TX200-TR101, a **cell therapy** solution for infusion, in patients who have previously received this therapy in a prior study. The trial is a long-term follow-up study, focusing on patients with a history of **kidney transplant rejection**. The study is structured as a non-randomized, open-label trial, with an estimated duration extending until September 2039. Participants will be involved in the study from the recruitment start date in August 2023, with the length of individual participation varying based on their previous involvement in the initial study.

Study visits are sequenced to include an initial screening visit, where eligibility is confirmed based on criteria such as prior enrollment in the Phase I/IIa study TX200-KT02 and the ability to provide informed consent. Follow-up visits will be conducted periodically to monitor the long-term safety and tolerability of the TX200-TR101 infusion, with assessments including the incidence of serious adverse events (SAEs) and overall survival. Secondary endpoints will evaluate the incidence of graft rejection, anti-drug antibodies, graft loss, and chronic graft dysfunction. The end-of-study visit will conclude the participant's involvement, summarizing the long-term outcomes and any adverse events experienced.

Participants are expected to remain in the study for its full duration unless conditions arise that necessitate early termination, such as withdrawal of consent or significant adverse events. The trial's primary objective is to ensure the long-term safety of the TX200-TR101 infusion, with data collected contributing to the understanding of its effects in the context of kidney transplant rejection. The study adheres to ethical guidelines and regulatory requirements, ensuring that all procedures are conducted with the utmost care and scientific rigor.

The clinical trial involves the administration of **TX200-TR101**, an experimental medication classified as a **Structurally Diverse Substance - Cell therapy**. This investigational product is provided in the form of a **solution for infusion**. The administration route is **intravenous use**, ensuring direct delivery into the bloodstream. The trial is designed to evaluate the safety and tolerability of TX200-TR101, with a focus on the incidence of serious adverse events as per CTCAE V5.0 guidelines. The maximum treatment period for the administration of TX200-TR101 is set at one day, with no specified maximum daily or total dose amount, indicating that dosing is determined based on individual patient needs and clinical judgment.

TX200-TR101 is an **autologous antigen-specific chimeric antigen receptor T regulatory cell therapy** (CAR-Treg therapy), developed by Sangamo Therapeutics France SAS. This therapy is designated as an orphan drug, highlighting its potential use in treating rare conditions. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the safety profile of the investigational product.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the long-term safety and tolerability of the **TX200-TR101** infusion, evaluated by overall survival and the incidence of serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary endpoints include the incidence of graft rejection according to the Banff classification criteria, the incidence of anti-drug antibodies against HLA A2 CAR Tregs, the incidence of graft loss due to rejection, and the incidence of chronic graft dysfunction measured by changes in estimated glomerular filtration rate.

The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial duration, which is estimated to conclude by September 4, 2039. The trial will involve the use of validated scales and laboratory tests to ensure the accuracy and reliability of the data collected. The endpoints are designed to provide comprehensive insights into the efficacy of the **TX200-TR101** therapy in maintaining graft function and patient survival over the long term.