Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment
Phase I- II clinical trial to evaluate the feasibility of the method and the absence of relevant side effects derived from product implant.
HYPOTHESIS: Once designed the nanostructured artificial human corneas by the Tissue Engineering Group of the University of Granada, and after evaluating their suitable properties ex vivo and their in vivo utility by means of anterior lamellar keratoplasty in laboratory animals, it is necessary to proceed to clinical evaluation in human patients suffering from severe corneal pathology. The results obtained during pre-clinical study, both in laboratory and in experimental animals, suggest that nanostructured artificial human corneas could help to treat various corneal diseases that occur with any substance loss or serious structural alteration, with no relevant side effects.
Other: Anterior lamellar nanostructured artificial human cornea.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter Clinical Trial to Evaluate the Safety and Feasibility of an Allogeneic Tissue Engineered Drug (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers Refractory to Conventional Treatment|
- Appearance of adverse events and serious adverse events related to treatment. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
- Persistence of the ulcer or regeneration / repair of the corneal stroma. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Visual acuity. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Corneal transparency [ Time Frame: 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||January 2019 (Final data collection date for primary outcome measure)|
Experimental: Anterior lamellar nanostructured artificial human cornea
Anterior lamellar nanostructured artificial human cornea with allogenic from dead donor and cultured in its inside and allogeneic corneal epithelium cultured in its surface
Other: Anterior lamellar nanostructured artificial human cornea.
Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors and biomaterials
No Intervention: Amniotic membrane transplantation
Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.
Phase I-II, controlled, randomized, multicenter clinical trial. The total number of patients to be included is 20. In an initial phase, will be included 5 patients sequentially (be subjected to the experimental treatment), with a month and a half safety period between patients.
At random, 5 of these patients will be implanted cornea and 10 control patients will receive an amniotic membrane transplant as conventional treatment of corneal trophic ulcers in advanced stages.
The study population consists of patients with severe corneal pathology (corneal ulcers refractory to conventional trophic treatment or sequels of previous ulcers having stromal fibrosis and / or limbal failure in the same eye) for which, there isn't currently an effective alternative therapeutic
It is estimated that the inclusion period is approximately 36 months, and a follow-up period of 24 months for each patient. Thus the total duration of the study will be about 60 months from the inclusion of the first patient until the end of the follow-up period of the last patient included.
To all patients enrolled in the trial, assigned to the experimental group will proceed to be implanted an anterior lamellar nanostructured artificial cornea with allogeneic cells from dead donors and biomaterials.
The implant of this Advanced Therapy drug will cover defects or structural alterations existing in the affected cornea. In this phase of the study, it is aimed to assess the feasibility of the procedure and the biosafety of the implant once grafted in the patient's cornea.
Patients who are randomized to the control group will be subjected to the usual treatment of their condition, consisting of amniotic membrane transplantation
Once the artificial corneal graft or amniotic membrane transplantation in the affected eye is completed, will proceed with the monitoring and continuous assessment of each subject. For this, it will be used the usual revision methods used for the anterior pole of the eyeball in all hospitals involved in the study.
Main objective: To evaluate the safety, feasibility and evidence of clinical efficacy of an anterior lamellar nanostructured artificial human cornea model, in a group of patients with severe corneal disease, for whom there are currently no effective therapeutic alternative.
- To generate lamellar nanostructured artificial human corneas of allogeneic origin of dead donor, from sclerocorneal limbus and agarose-fibrin biomaterials.
- To implant the nanostructured artificial human corneas of allogeneic origin of dead donor in a group of patients randomized to the experimental group, suffering from severe corneal pathology as a graft in the wound bed.
- To assess Biosecurity the nanostructured artificial human corneas of allogeneic origin of dead donor implanted in patients to rule out relevant adverse reactions.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765244
|Contact: Ana Cardesa||0034 firstname.lastname@example.org|
|University Hospital Puerta del Mar||Recruiting|
|Cádiz, Spain, 11009|
|Contact: Belén Hoyos, MD, PhD 660409473 email@example.com|
|Principal Investigator: Belén Hoyos, MD, PhD|
|Sub-Investigator: María Jesús Cruz, MD, PhD|
|Sub-Investigator: Leticia Royo, MD, PhD|
|Sub-Investigator: Iratze Zabalza, Zabalza|
|University Hospital San Cecilio||Recruiting|
|Granada, Spain, 18012|
|Contact: Carmen González, MD, PhD 625486990 firstname.lastname@example.org|
|Sub-Investigator: Daniel Serrano, MD, PhD|
|Sub-Investigator: Inmaculada Domínguez, MD, PhD|
|Principal Investigator: Carmen González, MD, PhD|
|Sub-Investigator: José Ignacio Muñoz, MD, PhD|
|Sub-Investigator: José Luis García, MD, PhD|
|Sub-Investigator: Alberto Villarrubia, MD, PhD|
|University Hospital Virgen de las Nieves||Recruiting|
|Granada, Spain, 18014|
|Contact: Santiago Medialdea, MD, PhD 619271254 email@example.com|
|Principal Investigator: Santiago Medialdea, MD, PhD|
|Sub-Investigator: Daniel Martínez, MD, PhD|
|Sub-Investigator: José Lucena, MD, PhD|
|University Hospital Virgen Macarena||Recruiting|
|Sevilla, Spain, 41009|
|Contact: Beatriz Mataix, MD, PhD 955008696 firstname.lastname@example.org|
|Sub-Investigator: Jesús Montero, MD, PhD|
|Sub-Investigator: Almudena García, MD, PhD|
|Sub-Investigator: Manuél Caro, MD, PhD|
|University Hospital Virgen de Rocío||Recruiting|
|Sevilla, Spain, 41013|
|Contact: Juan Ramón del Trigo, MD, PhD 630926841 email@example.com|
|Principal Investigator: Juan Ramón del Trigo, MD, PhD|
|Sub-Investigator: Ana María Muñoz, MD, PhD|
|Sub-Investigator: Carmen Vázquez, MD, PhD|
|Study Chair:||Santiago Medialdea, MD, PhD||Hospital U Virgen de las Nieves|
|Study Chair:||Miguel Alaminos, MD, PhD||Universidad de Granada|