Evaluation of Allogenic Adipose-Derived Mesenchymal Stem Cells on Fibrin-Hyaluronic Matrix for Venous Ulcer Treatment in Lower Limbs

The primary objective of this clinical trial is to evaluate the **feasibility** and **safety** of using allogenic adipose-derived adult mesenchymal stem cells expanded on a fibrin-hyaluronic biological matrix for the treatment of venous ulcers of the lower limbs. This is clinically relevant as venous ulcers are a common and challenging condition to manage, often leading to chronic wounds and significant morbidity. The trial aims to determine whether this innovative treatment approach can be safely implemented and whether it is a viable option for improving patient outcomes.

Secondary objectives include:

• Determining the effect of the experimental treatment on wound closure time compared to the control group.
• Assessing the healing evolution of the lesion in terms of depth, size, type of edges, tissue, and exudate compared to the control group.
• Evaluating the effect on the concentration of growth factors related to wound healing, such as cytokines IL-6, IL-4, TGF-β1, and IL-10, in the lesion exudate at various time points, and its possible relationship with other efficacy parameters.
• Evaluating the evolution of pain associated with venous ulcers in the group treated with the experimental intervention compared to the control group.
• Determining the perceived quality of life after treatment with the experimental intervention compared to the control group.

The clinical trial focuses on evaluating the **feasibility and safety** of a treatment for **venous ulcers of the lower limbs**. The study population includes adults over the age of 18, encompassing both male and female participants. The trial does not involve a vulnerable population. Participants are required to have active or recurrent venous ulcers classified as C6 according to the CEAC clinical classification, with an ulcer area between 5-10 cm² and a Grade III injury on the Widmer scale. Additionally, participants must have palpable distal pulses in the lower limbs, with an Ankle-Brachial Index (ABI) between 0.8 and 1.3. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase I-II**, multicenter, randomized, controlled, proof-of-concept study designed to evaluate the feasibility, safety, and efficacy of using **allogenic adipose-derived adult mesenchymal stem cells expanded on fibrin-hyaluronic biological matrix** for the treatment of **venous ulcers of the lower limbs**. The trial will involve a series of study visits, beginning with an inclusion (screening) visit, where participants will be assessed for eligibility based on criteria such as age, presence of active or recurrent venous ulcers, and specific clinical measurements. Participants must be over 18 years of age, have a venous ulcer with an area between 5-10 cm², and meet other clinical criteria to be included in the study.

The trial is expected to commence recruitment on December 22, 2023, and is estimated to conclude by June 22, 2027. Participants will be randomly assigned to either the treatment group receiving the investigational medicinal product (IMP) or a control group. The study is double-blind, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The primary endpoints focus on the feasibility and safety of the treatment, while secondary endpoints include assessing the effect of the IMP on wound closure time, healing evolution, growth factor concentration, pain evolution, and perceived quality of life compared to the control group.

Participants will be involved in the study for the duration of the trial, with regular follow-up visits scheduled to monitor progress and collect data on the endpoints. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation where continued participation is deemed not in the participant's best interest. The trial's design and procedures are structured to ensure rigorous evaluation of the investigational product while maintaining participant safety and data integrity.

The clinical trial involves the use of an **experimental medication** known as the Bioengineered Artificial Mesenchymal Sheet (BAMS). This product is classified as a **living tissue equivalent** and is designed for **cutaneous use**. The active substance in BAMS consists of **allogenic adipose-derived adult mesenchymal stem cells** expanded on a fibrin-hyaluronic biological matrix. These stem cells are derived from adipose tissue and are expanded on a matrix that combines fibrin and hyaluronic acid, providing a supportive environment for cell growth and function. The BAMS is an advanced therapy medicinal product, specifically developed for the treatment of venous ulcers of the lower limbs. The administration of BAMS is performed topically, directly to the affected area, in accordance with the study protocol. The frequency and dosage of administration are determined by the trial's specific requirements and are monitored to ensure participant compliance.

In addition to the experimental treatment, the study may include the use of standard-of-care therapy as a comparator treatment. This involves the application of conventional wound care practices, which may include cleaning, dressing, and other supportive measures to manage venous ulcers. The inclusion of standard-of-care therapy allows for a controlled comparison to evaluate the efficacy and safety of the BAMS treatment. Participant compliance with both the experimental and non-experimental treatments is closely monitored throughout the trial to ensure adherence to the study protocol and to accurately assess the outcomes.

The clinical trial aims to assess the efficacy of **Allogenic adipose-derived adult mesenchymal stem cells expanded on fibrin-hyaluronic biological matrix** in the treatment of venous ulcers of the lower limbs. Efficacy will be evaluated through several secondary endpoints. These include the effect of the investigational medicinal product (IMP) on wound closure time compared to the control group, the healing evolution of the lesion, and the concentration of growth factors closely related to wound healing. Additionally, the trial will assess the evolution of pain derived from the presence of venous ulcers in the group treated with the IMP versus the control group, as well as the perceived quality of life after treatment with the IMP compared to the control group.