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

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ClinicalTrials.gov Identifier: NCT01765244
Recruitment Status : Recruiting
First Posted : January 10, 2013
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
Iniciativa Andaluza en Terapias Avanzadas
Information provided by (Responsible Party):
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

Brief Summary:
This is a prospective, phase I-II, randomised, open-label clinical trial that will evaluate the safety and feasibility, as well as clinical efficacy evidence, of a bioengineered anterior corneal substitute in adults with severe trophic corneal ulcers. This model of human anterior allogeneic cornea will provide an alternative approach in cases where human donor keratoplasty is not an option.

Condition or disease Intervention/treatment Phase
Severe Trophic Corneal Ulcers Refractory to Conventional Treatment Sequelae of Previous Trophic Corneal Ulcers Drug: Anterior lamellar nanostructured artificial human cornea. Other: Amniotic membrane transplantation Phase 1 Phase 2

Detailed Description:
This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in eleven Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of a bioengineered human anterior corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Bioengineered anterior human corneal substitute Amniotic membrane corneal graft
Masking: None (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
Actual Study Start Date : January 17, 2014
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Anterior lamellar nanostructured artificial human cornea.
Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold
Other Name: Bioengineered human anterior corneal substitute

Active Comparator: Amniotic membrane transplantation
Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.
Other: Amniotic membrane transplantation
Implantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique.




Primary Outcome Measures :
  1. Adverse events (and serious adverse events) causally related to experimental treatment. [ Time Frame: 24 months ]
  2. Implant status (integrity, detachment and reabsorption) [ Time Frame: 24 months ]
  3. Local, regional or systemic infections related with the implant [ Time Frame: 24 months ]
  4. Induced corneal neovascularization [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Ulcer persistency or relapse and corneal stromal repair [ Time Frame: 24 months ]
  2. Visual acuity [ Time Frame: 24 months ]
  3. Corneal transparency [ Time Frame: 24 months ]
  4. Tear function (TBUT and Schirmer) [ Time Frame: 24 months ]
  5. Quality of life (EQ-5) [ Time Frame: 24 months ]
  6. Induced chronic ocular complications [ Time Frame: 24 months ]
  7. In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM) [ Time Frame: 24 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Man or woman aged≥18, with no upper age limit.
  • Patients that give their informed consent for study participation.
  • Stage 3 Mackie corneal ulcers that do not respond to conventional medical treatment, or patients having undergone previous stage 3 Mackie corneal ulcers,33 currently suffering sequelae such as stromal fibrosis or corneal thinning, having no effective therapeutic alternative.
  • Stromal involvement, not reaching the Descemet membrane. Central or peripheral localization.
  • Minimum duration of the disease causing the corneal ulcer: 6 weeks.
  • No active ocular infection.
  • Patients with normal laboratory parameters as defined by: Leukocytes≥3000 cells/µL; Neutrophils≥1500 cells/µL; Platelets≥100 billion/L; AST/ALT≤1.5 ULN; Creatinine≤1.5 mg/dL.

Exclusion Criteria:

  • Absence of stromal involvement.
  • Good response to standard medical treatments for corneal disease in less than 3 to 5 weeks.
  • Bullous keratopathy or other endothelial decompensations.
  • Active ocular infection.
  • Positive serology to HBV, HCV, HIV or any other pathology that may interfere with correct patient follow-up.
  • Pregnant or breast-feeding women or childbearing-age women that do not consent the use of contraceptive methods approved in the protocol.
  • Medical history of active neoplasia within the past 5 years. Participation in other clinical trials in 3 months previous to inclusion, or in the previous 5 years for trials with advanced therapies.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01765244


Contacts
Contact: Juliana Martinez-Atienza, PhD 0034 955048278 juliana.martinez.ext@juntadeandalucia.es

Locations
Spain
Hospital San Juan de Dios Recruiting
Bormujos, Spain
Contact: Antonio Ruiz Montero, MD       anruizmontero@yahoo.es   
Principal Investigator: Antonio Ruiz Montero, MD         
University Hospital Puerta del Mar 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         
Hospital la Arruzafa Recruiting
Córdoba, Spain
Contact: Alberto Villarrubia Cuadrado, MD       alvillarrubia@hospitalarruzafa.com   
Principal Investigator: Alberto Villarrubia Cuadrado, MD         
Hospital Universitario Reina Sofía Recruiting
Córdoba, Spain
Contact: Jose María Gallardo Galera, MD       josem.gallardo.sspa@juntadeandalucia.es   
Principal Investigator: Jose María Gallardo Galera, MD         
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         
Hospital Costa del Sol Recruiting
Marbella, Spain
Contact: Yolanda Fernández Barrientos, MD       yfernandezbarrientos@gmail.com   
Principal Investigator: Yolanda Fernández Barrientos, MD         
Marina Rodriguez Calvo-Mora Recruiting
Málaga, Spain
Contact: Marina Rodriguez Calvo-Mora       marina.rodriguez.calvomora.sspa@juntadeandalucia.es   
Principal Investigator: Marina Rodriguez Calvo-Mora, MD         
University Hospital Virgen Macarena Recruiting
Sevilla, Spain, 41009
Contact: Beatriz Mataix, MD, PhD    955008696    b1mataix@yahoo.es   
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    deltrigo@telefonica.net   
Principal Investigator: Juan Ramón del Trigo, MD, PhD         
Sub-Investigator: Ana María Muñoz, MD, PhD         
Sub-Investigator: Carmen Vázquez, MD, PhD         
Hospital Nuestra Señora de Valme Recruiting
Sevilla, Spain
Contact: Ana García Bernal, MD       anagarbe@hotmail.com   
Principal Investigator: Ana García Bernal, MD         
Sponsors and Collaborators
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Iniciativa Andaluza en Terapias Avanzadas
Investigators
Study Director: Santiago Medialdea, MD, PhD Hospital U Virgen de las Nieves
Study Chair: Miguel Alaminos, MD, PhD Universidad de Granada

Additional Information:
Publications:
Responsible Party: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01765244     History of Changes
Other Study ID Numbers: CAH/Ulc/2010
2010-024290-40 ( EudraCT Number )
First Posted: January 10, 2013    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud:
Corneal trophic ulcers, limbal deficiency, cornea blindness

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