"Abdominal Aortic Aneurysm Stabilization with Truncal Cells: Controlled Clinical Trial with Historical Cohorts."

The primary objective of this clinical trial is to evaluate the **safety** and feasibility of an allogeneic adipose tissue-derived mesenchymal stem cell implantation in the sac of an abdominal aortic aneurysm treated by endoprosthesis. This is clinically relevant as it aims to assess the potential of mesenchymal stem cells to enhance the treatment outcomes of patients undergoing endovascular surgical repair for abdominal aortic aneurysms, potentially offering a novel therapeutic approach.

Secondary objectives include:

• Evaluating the preliminary efficacy of mesenchymal stem cell therapy in the stent-treated abdominal aortic aneurysm sac compared with a historical cohort with conventional endovascular treatment.
• Comparing the clinical evolution of patients undergoing endovascular surgical repair with infusion of mesenchymal stem cells into the aneurysm sac with the historical cohort.

The clinical trial involves participants diagnosed with **abdominal aortic aneurysm** who are undergoing endovascular surgical repair. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a good infrarenal neck suitable for the placement of a standard device and must have an estimated life expectancy of more than two years. Women of childbearing potential are required to have a negative pregnancy test at inclusion and must agree to use highly effective contraceptive methods during the study. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to attend all study visits and comply with all study procedures. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and feasibility of an allogeneic adipose tissue-derived mesenchymal stem cell implantation in patients with an abdominal aortic aneurysm undergoing endovascular surgical repair. This is a Phase 4, single-center, controlled trial utilizing historical cohorts for comparison. The study employs a randomized, double-blind methodology to ensure unbiased results. The trial is expected to commence on February 1, 2024, and conclude by February 1, 2026, with an estimated duration of two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as aneurysm size, age, and life expectancy. The inclusion visit will also involve a negative pregnancy test for women of childbearing potential and agreement to use effective contraceptive methods. Following the initial screening, participants will attend regular follow-up visits to monitor the occurrence of procedure-related adverse events and the efficacy of the treatment, including imaging tests to assess aneurysm size reduction. The end-of-study visit will evaluate the primary and secondary endpoints, including the proportion of adverse events and changes in quality of life.

The expected length of participant involvement is approximately 12 months, with conditions for early termination including the inability to attend study visits or adhere to study procedures. The primary endpoints focus on the proportion of procedure-related adverse events and major adverse cerebral and cardiovascular events within 12 months post-treatment. Secondary endpoints include the reduction in aneurysm sac size, stent migration, presence of leaks, reoperation rates, hospital admission rates, and changes in quality of life. The investigational product, a **solution for injection** of allogeneic adipose-derived mesenchymal stem cells, will be administered with a maximum daily dose of 1,000,000 cells, ensuring the treatment period does not exceed one day.

The clinical trial involves the administration of **allogeneic adipose-derived mesenchymal stem cells expanded** (e-ASCs) as the experimental treatment. These cells are provided in the form of a **solution for injection**. The administration route is via **injection** directly into the target area. The maximum daily dose is set at 1,000,000 cells, with the same amount being the maximum total dose allowed for the treatment period. The treatment is designed to be administered over a maximum period of one day. The cells are derived from adipose tissue and are expanded to increase their therapeutic potential. The product is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the safety and feasibility of the e-ASCs implantation in the sac of an abdominal aortic aneurysm treated by endoprosthesis. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial aims to provide insights into the potential benefits of this cell therapy in stabilizing abdominal aortic aneurysms.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints focus on safety-related measures, including the proportion of procedure-related adverse events, adverse events related to the infusion of **allogeneic adipose tissue-derived mesenchymal stem cells**, and the incidence of major adverse cerebral and cardiovascular events (MACCE) within 12 months post-treatment. These endpoints will be monitored throughout the study duration to evaluate the safety profile of the intervention.

Secondary endpoints are designed to assess the efficacy of the treatment in terms of anatomical and clinical outcomes. These include the reduction in the size of the aneurysm sac as observed in imaging tests such as CT and Doppler echo, with a significant reduction defined as a decrease of 5mm or more over six months. Additional secondary endpoints include the percentage of patients experiencing stent migration, presence of leaks on control CT at 1 month and 1 year, reoperation rates, and hospital admission rates, all compared to a historical cohort. Furthermore, changes in quality of life will be evaluated using a specific survey administered at one month and one year post-treatment, with a 10% change in scores considered clinically relevant. These assessments will provide a comprehensive evaluation of the treatment's impact on patient outcomes.