Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.

Phase I-IIa, Randomized, Controlled, Open-label, Single-center Clinical Trial to Evaluate Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Patients With Cleft Palate

Phase I/II, controlled, open-label, randomized, single site clinical trial to assess the safety and feasibility, as well as hint efficacy evidence of a bioengineered palate mucosa substitute on nanostructured fibrin-agarose scaffolds with autologous mucosa tissue-specific cells (culture-expanded fibroblasts and keratinocytes), for tissue replacement and repair of donor area after the reconstruction of palate cleft defects (staphylorraphy), in comparison with standard care for donor mucosa.

Study Overview

• Status: Recruiting
• Conditions: Cleft Lip and Palate
• Intervention / Treatment: Procedure: implantation with an autologous human palatal mucosa substitute made of nanostructured fibrin-agarose generated by tissue engineering (BIOCLEFT).

Detailed Description

The initial phase of the trial is non-randomized, and involves the sequential recruitment of 5 eligible subjects with a minimum safety period of 30 days between them. All of them will be implanted with the autologous human palatal mucosa substitute of nanostructured fibrin-agarose generated by tissue engineering (BIOCLEFT), after reconstruction of the palate. Once the 5th treated patient has reached 1.5 months of follow-up after the intervention (Visit 8), the safety and feasibility data analysis will be carried out by the Independent Data Safety and Monitoring Committee (interim analysis), after which will allow continuation to the randomized phase of the trial, if the results allow it.

In the second phase, the rest of the patients (10) will be recruited, who will be randomized 1:1, such that 5 of these patients will be implanted with the investigational medication while undergoing standard surgical reconstruction. (uranostaphyllorrhaphy), while the other 5 will only undergo standard surgical reconstruction and will constitute the control group.

The total number of patients to be included in the study will be 15, who will be followed for 24 months according to a protocolized scheme that includes 2 pre-implant visits, 1 implant visit and 9 post-implant evaluation visits.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Elisa Cubiles; Phone Number: 955048278; Email: emontero@fibao.es
• Study Contact Backup: Name: Soraya Santana; Phone Number: 618 93 00 77; Email: ssantana@fibao.es

Study Locations

• Spain
  • Spain/Granada
    • Granada, Spain/Granada, Spain, 18014
      • Recruiting
      • University Hospital Virgen de las Nieves
      • Contact: Ricardo Fernández, MD,PhD; Phone Number: 671 593 192; Email: rfdezvalades@me.com
      • Contact: Miguel Alaminos, MD, PhD; Phone Number: 20461 958 241000; Email: malaminos@ugr.es
      • Principal Investigator: Ricardo Fernández, MD,PhD
      • Sub-Investigator: Antonio España, MD,PhD
      • Sub-Investigator: Esther Liceras, MD, PhD
      • Sub-Investigator: Daniel Vallejo, MD, PhD
      • Sub-Investigator: Adoración Martínez, MD, PhD
      • Sub-Investigator: Ana Marín, MD, PhD
      • Sub-Investigator: Rosario Cortés, MD, PhD
      • Sub-Investigator: Belén Pérez, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pediatric patients, of both sexes.
• Diagnosis of total unilateral non-syndromic cleft lip and palate (FLPNS) that will undergo surgery for correction.
• Children who have previously donated a sample of oral mucosa during the cleft lip repair procedure (cheiloplasty).
• Informed consent signed by one or both parents (or legal guardian) adequately informed of the study and willing to follow the trial procedures and instructions.

Exclusion Criteria:

• Active infectious diseases.
• Allergies or hypersensitivity to any of the components/excipients of the Investigational Product.
• Severe hematological disorders/blood dyscrasias.
• Severe hepatic or renal dysfunction/failure.
• Serious endocrine disorders/dysfunctions.
• Malignant neoplasms
• Active HIV, HBV or HCV infection.
• Metabolic bone diseases (Paget's disease, hypercalcemia, etc.).
• Children with cleft lip and palate who present other congenital malformations that, in the opinion of the researcher, could affect the result of the study or the interpretation of the results of the study.
• Any other pathology that in the opinion of the investigator should not be included in the study for other medical or social reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental; The experimental group will be implanted with an autologous human palatal mucosa substitute made of nanostructured fibrin-agarose generated by tissue engineering (BIOCLEFT). The implantation of this advanced therapy medication will cover the lateral defect generated by the mobilization of fibromucous flaps during standard surgery (uranostaphylorrhaphy	Procedure: implantation with an autologous human palatal mucosa substitute made of nanostructured fibrin-agarose generated by tissue engineering (BIOCLEFT).; cleft palate repair surgery, all patients in the study will receive the standard treatment (uranostaphyllorrhaphy), with the only difference that patients assigned to the experimental study group will additionally have BIOCLEFT tissue obtained through tissue engineering grafted onto them. the lateral area of the palatine bone exposed when mobilizing the flaps. For the implant, the BIOCLEFT fabric will be placed in the area of exposed bone, sized to the size of the defect and sutured using uncoated, monofilament long-term absorbable synthetic suture.
No Intervention: control group; These patients will be included in the control group and will receive the usual treatment for their disease (uranoestafilorrafia), without applying any type of restriction to the area used for the movement of the arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate implant´s feasibility and appearance of adverse events and serious adverse events related to treatment	Incidence of Serious Adverse Events after at the time of the implant of study drug.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the time of the regeneration and healing of the lateral defect of the palatine bone from the moment of the intervention		24 months
Evaluation of the aesthetic result through analysis of photographs	A scale designed ad hoc for the present trial will be used (aesthetic appearance assessment scale)	24 months
Preliminary evaluation of craniofacial growth through analysis of craniofacial photographs		24 months
Hearing evaluation	Otoscopic/otomicroscopic examination and tympanogram by the otorhinolaryngologist, and placement of aeration tubes if considered necessary. The need or not to perform follow-up during the trial visits will be assessed depending on whether or not the patient presents any type of pathology.	24 months
Quality of life evaluation	Changes in quality of life will be assessed through the TAPQOL questionnaire for children between 1-5 years old.	24 months
Functional evaluation by the speech therapist	Evaluation of nasal escape; palate mobility; swallowing and articulation of functional language by the speech therapist.	24 months

Collaborators and Investigators

• Sponsor: Elisa María Cubiles Montero de Espinosa
• Collaborators: Andalusian Network for Design and Translation of Advanced Therapies

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): April 17, 2028
• Study Completion (Estimated): December 17, 2028

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Musculoskeletal Diseases; Stomatognathic Diseases; Mouth Diseases; Lip Diseases; Mouth Abnormalities; Stomatognathic System Abnormalities; Jaw Abnormalities; Jaw Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Cleft Palate; Cleft Lip
• Other Study ID Numbers: FIB-BIO-2023-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No