Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment
Study Details
Study Description
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 |
|---|---|---|
|
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 Design
Arms and Interventions
| 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 Names:
|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Adverse events (and serious adverse events) causally related to experimental treatment. [24 months]
- Implant status (integrity, detachment and reabsorption) [24 months]
- Local, regional or systemic infections related with the implant [24 months]
- Induced corneal neovascularization [24 months]
Secondary Outcome Measures
- Ulcer persistency or relapse and corneal stromal repair [24 months]
- Visual acuity [24 months]
- Corneal transparency [24 months]
- Tear function (TBUT and Schirmer) [24 months]
- Quality of life (EQ-5) [24 months]
- Induced chronic ocular complications [24 months]
- In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM) [24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Man or woman aged≥18, with no upper age limit.
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Patients that give their informed consent for study participation.
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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.
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Stromal involvement, not reaching the Descemet membrane. Central or peripheral localization.
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Minimum duration of the disease causing the corneal ulcer: 6 weeks.
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No active ocular infection.
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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:
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Absence of stromal involvement.
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Good response to standard medical treatments for corneal disease in less than 3 to 5 weeks.
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Bullous keratopathy or other endothelial decompensations.
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Active ocular infection.
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Positive serology to HBV, HCV, HIV or any other pathology that may interfere with correct patient follow-up.
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Pregnant or breast-feeding women or childbearing-age women that do not consent the use of contraceptive methods approved in the protocol.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital San Juan de Dios | Bormujos | Spain | ||
| 2 | University Hospital Puerta del Mar | Cádiz | Spain | 11009 | |
| 3 | Hospital la Arruzafa | Córdoba | Spain | ||
| 4 | Hospital Universitario Reina Sofía | Córdoba | Spain | ||
| 5 | University Hospital San Cecilio | Granada | Spain | 18012 | |
| 6 | University Hospital Virgen de las Nieves | Granada | Spain | 18014 | |
| 7 | Hospital Costa del Sol | Marbella | Spain | ||
| 8 | Marina Rodriguez Calvo-Mora | Málaga | Spain | ||
| 9 | University Hospital Virgen Macarena | Sevilla | Spain | 41009 | |
| 10 | University Hospital Virgen de Rocío | Sevilla | Spain | 41013 | |
| 11 | Hospital Nuestra Señora de Valme | Sevilla | Spain |
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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- CAH/Ulc/2010
- 2010-024290-40