Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Fundación Pública Andaluza Progreso y Salud
Sponsor:
Collaborator:
Iniciativa Andaluza en Terapias Avanzadas
Information provided by (Responsible Party):
Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT01765244
First received: January 9, 2013
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Corneal Ulcer
Other: Anterior lamellar nanostructured artificial human cornea.
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Appearance of adverse events and serious adverse events related to treatment. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: January 2014
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

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 conventional treatment of corneal trophic ulcers in advanced stages.

The study population consists of patients with corneal trophic ulcers refractory to conventional treatment attending the ophthalmology departments involved in this research project.

It is estimated that the inclusion period is approximately 24 months, and a follow-up period of 24 months for each patient. Thus the total duration of the study will be about 48 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.

Secondary objectives:

  • 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who give informed consent to participate in the study.
  • Presence of corneal ulcers Mackie stage 3 not responding to conventional medical treatment, besides being secondary to any of the specified causes : Riley-Day syndrome, Goldenhar-Gorlin syndrome, Mobius Syndrome, Corneal hypoesthesia family, Diabetes, Multiple Sclerosis, Leprosy, Hypovitaminosis A, Acoustic neuroma, Meningioma, Neuralgia, Aneurysm, Ictus, Neoplasia, Simple herpes, Zoster herpes, Caustic burns, Injury, inflammation, or wear contact lenses, Cataract surgery or keratoplasty, Topical anesthetics abuse, Toxicity of timolol, betaxolol, diclofenac sodium or sulfacetamide, Lattice or granular, Orbital neoplasia.
  • Stromal involvement should exist, but with a depth not reaching the Descemet's membrane. The location may be central and / or peripheral.
  • No active ocular infection.
  • Patients of both sexes over 18 years; no upper age limit exist
  • Duration of the disease causing the corneal ulcer equal or superior to six weeks.
  • Patients with normal laboratory parameters, defined by:

    1. Leukocytes ≥ 3000
    2. Neutrophils ≥ 1500
    3. Platelets ≥ 100,000
    4. Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤ 1.5 standard range institution
    5. Creatinine ≤ 1.5 mg / dl

Exclusion Criteria:

  • Absence of stromal involvement (eg persistent epithelial defects).
  • Corneal Pathology responding properly to standard medical treatments in a shorter period of 3-5 weeks.
  • Active ocular infection.
  • Positive serology for Hepatitis B virus (HBV), Hepatitis B virus (HCV), Immunodeficiency human virus (HIV) or other coexisting pathology that, in the opinion of the investigator, would prevent from monitoring patients in the trial.
  • Pregnant or lactating women or women of childbearing potential not using a proven efficacy contraceptive method. It is described as highly effective contraceptive method that oral contraceptive one (combining estrogen with progestin) or any other such as, for example, an injectable hormonal contraceptive, implantable or patch, intrauterine device (IUD) or surgical sterilization (provided that hormonal contraceptives do not interact with the drug in research
  • History of neoplasia except for orbital neoplasia.
  • Patients who participated in the last 3 months prior to study inclusion in a clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765244

Contacts
Contact: Ana Cardesa 0034 955019040 ana.cardesa@juntadeandalucia.es

Locations
Spain
University Hospital Puerta del Mar Not yet recruiting
Cádiz, Spain, 11009
Contact: Belén Hoyos, MD, PhD    660409473    belenhoyossanabria@gmail.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    carmengonzalez23283@hotmail.com   
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    santiago.medialdea.sspa@juntadeandalucia.es   
Principal Investigator: Santiago Medialdea, MD, PhD         
Sub-Investigator: Daniel Martínez, MD, PhD         
Sub-Investigator: José Lucena, MD, PhD         
University Hospital Virgen de Rocío Not yet recruiting
Sevilla, Spain, 41013
Contact: Juan Ramón del Trigo, MD, PhD    630926841    deltrigo@telefonica.net   
Principal Investigator: Juan Ramón del Trigo, MD, PhD         
Sub-Investigator: Ana María Muñoz, MD, PhD         
Sub-Investigator: Carmen Vázquez, MD, PhD         
University Hospital Virgen Macarena Not yet recruiting
Sevilla, Spain, 41009
Contact: Ignacio Montero, MD, PhD    955008696    l_morillo@hotmail.com   
Sub-Investigator: María Dolores Morillo, MD, PhD         
Sponsors and Collaborators
Fundación Pública Andaluza Progreso y Salud
Iniciativa Andaluza en Terapias Avanzadas
Investigators
Study Chair: Miguel González, MD, PhD University Hospital San Cecilio
Study Chair: Miguel Alaminos, MD, PhD Universidad de Granada
  More Information

Additional Information:
No publications provided

Responsible Party: Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01765244     History of Changes
Other Study ID Numbers: CAH/Ulc/2010, 2010-024290-40
Study First Received: January 9, 2013
Last Updated: September 2, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Fundación Pública Andaluza Progreso y Salud:
Corneal trophic ulcers

Additional relevant MeSH terms:
Corneal Ulcer
Ulcer
Corneal Diseases
Eye Diseases
Eye Infections
Infection
Keratitis
Pathologic Processes

ClinicalTrials.gov processed this record on October 22, 2014