Evaluation of Autologous Tissue-Engineered Fibrin-Agarose Oral Mucosa Substitute in Cleft Palate Treatment: A Phase I-IIa Randomized Controlled Trial

The primary objective of this clinical trial is to evaluate the **safety** and **feasibility** of using an autologous tissue-engineered nanostructured fibrin-agarose human palatal mucosa substitute in the treatment of patients with cleft palate. This is clinically relevant as it aims to establish a novel therapeutic approach that could potentially improve surgical outcomes and reduce complications associated with traditional treatments for cleft palate.

Secondary objectives include assessing the use of BIOCLEFT in the treatment of patients with cleft palate by evaluating the clinical evolution of several parameters in comparison with a control group. These parameters include regeneration and healing, aesthetic appearance, craniofacial growth, hearing evaluation, speech therapy outcomes, and overall quality of life. These assessments are crucial for understanding the broader impact of the treatment on patient health and well-being.

The clinical trial involves **paediatric patients** diagnosed with non-syndromic total unilateral **cleft lip and palate** who are scheduled for surgical correction. The study population includes both male and female subjects, with an age range corresponding to children. Participants have previously donated an oral mucosa sample during the cleft lip repair procedure, known as cheiloplasty. The trial does not focus on a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is a **Phase I-IIa**, randomized, controlled, open-label, single-center study designed to evaluate the safety, feasibility, and evidence of efficacy of an autologous tissue-engineered nanostructured fibrin-agarose oral mucosa substitute for the treatment of **cleft lip and palate**. The trial will involve pediatric patients diagnosed with non-syndromic total unilateral cleft lip and palate who are scheduled for corrective surgery. The study will commence with a screening visit to confirm eligibility based on the inclusion criteria, which require prior donation of an oral mucosa sample during a previous cheiloplasty procedure and informed consent from parents or legal guardians.

Participants will be randomly assigned to receive the investigational product, which consists of **autologous oral mucosa-derived adult keratinocytes and fibroblasts**, ex-vivo expanded and implanted in a biological fibrin-agarose matrix. The primary endpoints include assessing the feasibility of the surgical implantation in at least three out of five patients in the initial phase, as well as monitoring for any adverse events related to the treatment. Secondary endpoints will focus on indications of efficacy, such as regeneration and healing, aesthetic appearance, craniofacial growth, hearing evaluation, speech therapy outcomes, and quality of life.

The trial is expected to last until November 15, 2027, with participant involvement extending from the initial screening visit through to the end-of-study visit. Follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with specific attention to any adverse events. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or non-compliance with study procedures. The trial aims to provide valuable insights into the potential benefits of this advanced therapy product for patients with cleft palate.

The clinical trial involves the use of an **experimental medication** known as "Autologous oral mucosa differentiated adult keratinocytes and fibroblasts, expanded in a biological fibrin-agarose matrix." This product is classified as a **living tissue equivalent** and is an advanced therapy product. The active substances in this medication are **autologous oral mucosa-derived adult keratinocytes** and **autologous oral mucosa-derived adult fibroblasts**, both of which are ex-vivo expanded. The pharmaceutical form of this product is a living tissue equivalent, and it is administered via **implantation**. The medication is not a pediatric formulation and is not classified as an orphan drug. The product is developed by the Fundación para la Investigación Biosanitaria de Andalucía Oriental - Alejandro Otero (FIBAO).

In this study, the experimental treatment is compared against standard-of-care therapy for patients with cleft palate. The trial is designed to evaluate the safety, feasibility, and preliminary efficacy of the autologous tissue-engineered nanostructured fibrin-agarose oral mucosa substitute. The trial is a Phase I-IIa, randomized, controlled, open-label, single-center study. The primary objective is to assess the safety and feasibility of the treatment, with a focus on its application in human palatal mucosa. Participant compliance with the treatment regimen will be monitored throughout the study to ensure adherence to the dosing schedule and administration protocol.

Efficacy in this clinical trial will be assessed through a combination of primary endpoints, focusing on the **feasibility** and safety of the treatment, as well as indications of efficacy in terms of regeneration and healing. The primary endpoints include the successful surgical implantation of the BIOCLEFT in at least 3 out of 5 patients in the initial phase, the occurrence of any adverse events, and specific assessments related to treatment. These assessments will cover aspects such as aesthetic appearance, craniofacial growth, hearing evaluation, speech therapy, and quality of life. The trial is designed to evaluate the use of an autologous tissue-engineered nanostructured fibrin-agarose oral mucosa substitute for human palatal mucosa in the treatment of patients with cleft palate.