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

Phase 1

Completed

• Conditions: Severe Trophic Corneal Ulcers Refractory to Conventional Treatment; Sequelae of Previous Trophic Corneal Ulcers
• Interventions: Drug: Anterior lamellar nanostructured artificial human cornea.; Other: Amniotic membrane transplantation

• Registration Number: NCT01765244
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2013-01-09
• Study First Submitted QC: 2013-01-09
• Study First Posted: 2013-01-10
• Study Start: 2014-01-17
• Status Verified: 2021-01
• Primary Completion: 2021-01-14
• Study Completion: 2021-01-14
• Last Update Submitted: 2021-01-19
• Last Update Posted: 2021-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anterior lamellar nanostructured artificial human cornea	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
Amniotic membrane transplantation	Amniotic membrane transplantation	Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.

Primary Outcome Measures

Name	Time	Method
Local, regional or systemic infections related with the implant	24 months
Implant status (integrity, detachment and reabsorption)	24 months
Adverse events (and serious adverse events) causally related to experimental treatment.	24 months
Induced corneal neovascularization	24 months

Secondary Outcome Measures

Name	Time	Method
Quality of life (EQ-5)	24 months
Visual acuity	24 months
Corneal transparency	24 months
Tear function (TBUT and Schirmer)	24 months
Induced chronic ocular complications	24 months
Ulcer persistency or relapse and corneal stromal repair	24 months
In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)	24 months

Trial Locations

Locations (11)

Hospital Costa del Sol; 🇪🇸 Marbella, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

Marina Rodriguez Calvo-Mora; 🇪🇸 Málaga, Spain

University Hospital Virgen Macarena; 🇪🇸 Sevilla, Spain

University Hospital San Cecilio; 🇪🇸 Granada, Spain

University Hospital Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital San Juan de Dios; 🇪🇸 Bormujos, Spain

Hospital Nuestra Señora de Valme; 🇪🇸 Sevilla, Spain

Hospital la Arruzafa; 🇪🇸 Córdoba, Spain

University Hospital Puerta del Mar; 🇪🇸 Cádiz, Spain

University Hospital Virgen de Rocío; 🇪🇸 Sevilla, Spain